Full text data of KIF22
KIF22
(KID, KNSL4)
[Confidence: low (only semi-automatic identification from reviews)]
Kinesin-like protein KIF22 (Kinesin-like DNA-binding protein; Kinesin-like protein 4)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Kinesin-like protein KIF22 (Kinesin-like DNA-binding protein; Kinesin-like protein 4)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q14807
ID KIF22_HUMAN Reviewed; 665 AA.
AC Q14807; B2R5M0; B7Z265; O60845; O94814; Q53F58; Q9BT46;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-SEP-2001, sequence version 5.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=Kinesin-like protein KIF22;
DE AltName: Full=Kinesin-like DNA-binding protein;
DE AltName: Full=Kinesin-like protein 4;
GN Name=KIF22; Synonyms=KID, KNSL4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8599929;
RA Tokai N., Fujimoto-Nishiyama A., Toyoshima Y., Yonemura S.,
RA Tsukita S., Inoue J., Yamamoto T.;
RT "Kid, a novel kinesin-like DNA binding protein, is localized to
RT chromosomes and the mitotic spindle.";
RL EMBO J. 15:457-467(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9790757; DOI=10.1006/geno.1998.5452;
RA Song J., Murakami H., Yang Z.Q., Koga C., Adati N., Murata T.,
RA Geltinger C., Saito-Ohara F., Ikeuchi T., Matsumura M., Itakura K.,
RA Kanazawa I., Sun K., Yokoyama K.K.;
RT "Human genes for KNSL4 and MAZ are located close to one another on
RT chromosome 16p11.2.";
RL Genomics 52:374-377(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Adrenal gland, Amygdala, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney epithelium;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R.,
RA Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L.,
RA Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E.,
RA Harris P.C., Venter J.C., Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from
RT human chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP INTERACTION WITH SIAH1, AND DEGRADATION.
RX PubMed=11146551; DOI=10.1038/sj.onc.1204002;
RA Germani A., Bruzzoni-Giovanelli H., Fellous A., Gisselbrecht S.,
RA Varin-Blank N., Calvo F.;
RT "SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by
RT the proteasome pathway during mitosis.";
RL Oncogene 19:5997-6006(2000).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-452, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [12]
RP INTERACTION WITH FAM83D.
RX PubMed=18485706; DOI=10.1016/j.cub.2008.04.041;
RA Santamaria A., Nagel S., Sillje H.H.W., Nigg E.A.;
RT "The spindle protein CHICA mediates localization of the chromokinesin
RT Kid to the mitotic spindle.";
RL Curr. Biol. 18:723-729(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412 AND SER-427, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412 AND SER-427, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412; SER-543; SER-562
RP AND SER-581, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP TISSUE SPECIFICITY, VARIANTS SEMDJL2 SER-148; LEU-148 AND GLN-149, AND
RP VARIANT GLN-232.
RX PubMed=22152677; DOI=10.1016/j.ajhg.2011.10.015;
RA Min B.J., Kim N., Chung T., Kim O.H., Nishimura G., Chung C.Y.,
RA Song H.R., Kim H.W., Lee H.R., Kim J., Kang T.H., Seo M.E., Yang S.D.,
RA Kim D.H., Lee S.B., Kim J.I., Seo J.S., Choi J.Y., Kang D., Kim D.,
RA Park W.Y., Cho T.J.;
RT "Whole-exome sequencing identifies mutations of KIF22 in
RT spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic
RT type.";
RL Am. J. Hum. Genet. 89:760-766(2011).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP STRUCTURE BY NMR OF 570-660.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RSGI RUH-070, a C-terminal domain of kinesin-
RT like protein KIF22 from human.";
RL Submitted (AUG-2007) to the PDB data bank.
RN [20]
RP VARIANTS SEMDJL2 LEU-148; GLN-149 AND LEU-149.
RX PubMed=22152678; DOI=10.1016/j.ajhg.2011.10.016;
RA Boyden E.D., Campos-Xavier A.B., Kalamajski S., Cameron T.L.,
RA Suarez P., Tanackovic G., Andria G., Ballhausen D., Briggs M.D.,
RA Hartley C., Cohn D.H., Davidson H.R., Hall C., Ikegawa S., Jouk P.S.,
RA Konig R., Megarbane A., Nishimura G., Lachman R.S., Mortier G.,
RA Rimoin D.L., Rogers R.C., Rossi M., Sawada H., Scott R., Unger S.,
RA Valadares E.R., Bateman J.F., Warman M.L., Superti-Furga A.,
RA Bonafe L.;
RT "Recurrent dominant mutations affecting two adjacent residues in the
RT motor domain of the monomeric kinesin KIF22 result in skeletal
RT dysplasia and joint laxity.";
RL Am. J. Hum. Genet. 89:767-772(2011).
RN [21]
RP ERRATUM.
RA Boyden E.D., Campos-Xavier A.B., Kalamajski S., Cameron T.L.,
RA Suarez P., Tanackovic G., Andria G., Ballhausen D., Briggs M.D.,
RA Hartley C., Cohn D.H., Davidson H.R., Hall C., Ikegawa S., Jouk P.S.,
RA Konig R., Megarbane A., Nishimura G., Lachman R.S., Mortier G.,
RA Rimoin D.L., Rogers R.C., Rossi M., Sawada H., Scott R., Unger S.,
RA Valadares E.R., Bateman J.F., Warman M.L., Superti-Furga A.,
RA Bonafe L.;
RL Am. J. Hum. Genet. 90:170-170(2012).
CC -!- FUNCTION: Kinesin family that is involved in spindle formation and
CC the movements of chromosomes during mitosis and meiosis. Binds to
CC microtubules and to DNA.
CC -!- SUBUNIT: Interacts with FAM83D.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton (Probable).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14807-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14807-2; Sequence=VSP_046428;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in bone, cartilage, joint capsule,
CC ligament, skin, and primary cultured chondrocytes.
CC -!- PTM: Ubiquitinated; mediated by SIAH1 and leading to its
CC subsequent proteasomal degradation (Probable).
CC -!- DISEASE: Spondyloepimetaphyseal dysplasia with joint laxity, 2
CC (SEMDJL2) [MIM:603546]: A bone disease characterized by short
CC stature, distinctive midface retrusion, progressive knee
CC malalignment (genu valgum and/or varum), generalized ligamentous
CC laxity, and mild spinal deformity. Intellectual development is not
CC impaired. Radiographic characteristics include significantly
CC retarded epiphyseal ossification that evolves into epiphyseal
CC dysplasia and precocious osteoarthritis, metaphyseal
CC irregularities and vertical striations, constricted femoral neck,
CC slender metacarpals and metatarsals, and mild thoracolumbar
CC kyphosis or scoliosis with normal or mild platyspondyly. The most
CC distinctive features for differential diagnosis of SEMDJL2 are the
CC slender metacarpals and phalanges and the progressive degeneration
CC of carpal bones; however, these 2 features are evident only in
CC older children and young adults. The soft consistency of cartilage
CC in the airways leads to laryngotracheomalacia with proneness to
CC respiratory obstruction and inspiratory stridor in infancy and
CC childhood. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the kinesin-like protein family.
CC -!- SIMILARITY: Contains 1 kinesin-motor domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC08709.1; Type=Erroneous gene model prediction;
CC Sequence=EAW80007.1; Type=Erroneous gene model prediction;
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DR EMBL; AB017430; BAA33019.2; -; mRNA.
DR EMBL; AB017335; BAA33063.1; -; Genomic_DNA.
DR EMBL; BT007259; AAP35923.1; -; mRNA.
DR EMBL; AK294380; BAH11751.1; -; mRNA.
DR EMBL; AK312234; BAG35167.1; -; mRNA.
DR EMBL; AK316389; BAH14760.1; -; mRNA.
DR EMBL; AK223431; BAD97151.1; -; mRNA.
DR EMBL; AC002301; AAC08709.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC009133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471238; EAW80005.1; -; Genomic_DNA.
DR EMBL; CH471238; EAW80007.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC004352; AAH04352.1; -; mRNA.
DR EMBL; BC028155; AAH28155.1; -; mRNA.
DR RefSeq; NP_001243198.1; NM_001256269.1.
DR RefSeq; NP_001243199.1; NM_001256270.1.
DR RefSeq; NP_015556.1; NM_007317.2.
DR UniGene; Hs.612151; -.
DR PDB; 2EDU; NMR; -; A=570-660.
DR PDB; 3BFN; X-ray; 2.30 A; A=40-400.
DR PDBsum; 2EDU; -.
DR PDBsum; 3BFN; -.
DR ProteinModelPortal; Q14807; -.
DR SMR; Q14807; 40-369, 570-660.
DR IntAct; Q14807; 6.
DR MINT; MINT-156095; -.
DR STRING; 9606.ENSP00000160827; -.
DR ChEMBL; CHEMBL5470; -.
DR PhosphoSite; Q14807; -.
DR DMDM; 19863381; -.
DR PaxDb; Q14807; -.
DR PRIDE; Q14807; -.
DR DNASU; 3835; -.
DR Ensembl; ENST00000160827; ENSP00000160827; ENSG00000079616.
DR Ensembl; ENST00000400751; ENSP00000383562; ENSG00000079616.
DR Ensembl; ENST00000561482; ENSP00000454957; ENSG00000079616.
DR GeneID; 3835; -.
DR KEGG; hsa:3835; -.
DR UCSC; uc002dts.4; human.
DR CTD; 3835; -.
DR GeneCards; GC16P029802; -.
DR HGNC; HGNC:6391; KIF22.
DR HPA; HPA041076; -.
DR MIM; 603213; gene.
DR MIM; 603546; phenotype.
DR neXtProt; NX_Q14807; -.
DR Orphanet; 93360; Spondyloepimetaphyseal dysplasia with multiple dislocations.
DR PharmGKB; PA30180; -.
DR eggNOG; COG5059; -.
DR HOGENOM; HOG000007569; -.
DR HOVERGEN; HBG052252; -.
DR InParanoid; Q14807; -.
DR KO; K10403; -.
DR OMA; AGQRCGP; -.
DR OrthoDB; EOG7Z69BZ; -.
DR PhylomeDB; Q14807; -.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q14807; -.
DR EvolutionaryTrace; Q14807; -.
DR GeneWiki; KIF22; -.
DR GenomeRNAi; 3835; -.
DR NextBio; 15075; -.
DR PRO; PR:Q14807; -.
DR ArrayExpress; Q14807; -.
DR Bgee; Q14807; -.
DR CleanEx; HS_KIF22; -.
DR Genevestigator; Q14807; -.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0005871; C:kinesin complex; IEA:InterPro.
DR GO; GO:0000776; C:kinetochore; TAS:ProtInc.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005819; C:spindle; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0003777; F:microtubule motor activity; TAS:ProtInc.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0006281; P:DNA repair; IEA:InterPro.
DR GO; GO:0007018; P:microtubule-based movement; TAS:Reactome.
DR GO; GO:0007067; P:mitosis; TAS:ProtInc.
DR Gene3D; 3.40.850.10; -; 1.
DR InterPro; IPR003583; Hlx-hairpin-Hlx_DNA-bd_motif.
DR InterPro; IPR026986; KIF22.
DR InterPro; IPR027640; Kinesin-like_fam.
DR InterPro; IPR019821; Kinesin_motor_CS.
DR InterPro; IPR001752; Kinesin_motor_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR010994; RuvA_2-like.
DR PANTHER; PTHR24115; PTHR24115; 1.
DR PANTHER; PTHR24115:SF171; PTHR24115:SF171; 1.
DR Pfam; PF00225; Kinesin; 1.
DR PRINTS; PR00380; KINESINHEAVY.
DR SMART; SM00278; HhH1; 2.
DR SMART; SM00129; KISc; 1.
DR SUPFAM; SSF47781; SSF47781; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS00411; KINESIN_MOTOR_DOMAIN1; 1.
DR PROSITE; PS50067; KINESIN_MOTOR_DOMAIN2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Coiled coil;
KW Complete proteome; Cytoplasm; Cytoskeleton; Disease mutation;
KW DNA-binding; Dwarfism; Microtubule; Motor protein; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1 665 Kinesin-like protein KIF22.
FT /FTId=PRO_0000125433.
FT DOMAIN 40 299 Kinesin-motor.
FT NP_BIND 127 134 ATP (By similarity).
FT COILED 465 508 Potential.
FT MOD_RES 412 412 Phosphoserine.
FT MOD_RES 427 427 Phosphoserine.
FT MOD_RES 452 452 Phosphoserine.
FT MOD_RES 543 543 Phosphoserine.
FT MOD_RES 562 562 Phosphoserine.
FT MOD_RES 581 581 Phosphoserine.
FT VAR_SEQ 1 68 Missing (in isoform 2).
FT /FTId=VSP_046428.
FT VARIANT 148 148 P -> L (in SEMDJL2; dbSNP:rs193922921).
FT /FTId=VAR_067345.
FT VARIANT 148 148 P -> S (in SEMDJL2; dbSNP:rs193922920).
FT /FTId=VAR_067346.
FT VARIANT 149 149 R -> L (in SEMDJL2).
FT /FTId=VAR_067347.
FT VARIANT 149 149 R -> Q (in SEMDJL2; dbSNP:rs193922922).
FT /FTId=VAR_067348.
FT VARIANT 232 232 R -> Q.
FT /FTId=VAR_067349.
FT CONFLICT 24 24 Missing (in Ref. 2; BAA33063).
FT CONFLICT 122 122 S -> KV (in Ref. 2; BAA33063).
FT CONFLICT 135 169 HTMLGSPEQPGVIPRALMDLLQLTREEGAEGRPWA -> TH
FT AGQPRATWGDPAGSHGPPAAHKGGGCRGPAMG (in Ref.
FT 2).
FT CONFLICT 216 216 S -> N (in Ref. 5; BAD97151).
FT CONFLICT 270 270 L -> P (in Ref. 3; BAG35167).
FT CONFLICT 303 303 V -> A (in Ref. 2; BAA33063).
FT CONFLICT 381 381 H -> R (in Ref. 5; BAD97151).
FT CONFLICT 418 456 APASASQKLSPLQKLSSMDPAMLERLLSLDRLLASQGSQ
FT -> SSSLCLPETQPPTEAKAAWTRPCGAPPQLGPSACLPGE
FT P (in Ref. 2; BAA33063).
FT CONFLICT 505 513 ENHCPTMLR -> RTIVPQCSG (in Ref. 2;
FT BAA33063).
FT STRAND 45 50
FT STRAND 85 89
FT STRAND 91 94
FT HELIX 100 107
FT HELIX 109 111
FT HELIX 112 115
FT TURN 116 118
FT STRAND 121 127
FT HELIX 133 137
FT STRAND 141 144
FT HELIX 146 161
FT STRAND 167 180
FT STRAND 183 189
FT HELIX 218 228
FT HELIX 243 245
FT STRAND 246 260
FT STRAND 265 274
FT HELIX 299 312
FT HELIX 320 322
FT HELIX 324 328
FT TURN 329 331
FT STRAND 332 334
FT STRAND 338 345
FT HELIX 349 351
FT HELIX 352 362
FT STRAND 364 369
FT TURN 577 579
FT HELIX 582 598
FT HELIX 601 606
FT HELIX 612 625
FT HELIX 631 636
FT HELIX 642 658
SQ SEQUENCE 665 AA; 73262 MW; C6C0AC96741DD387 CRC64;
MAAGGSTQQR RREMAAASAA AISGAGRCRL SKIGATRRPP PARVRVAVRL RPFVDGTAGA
SDPPCVRGMD SCSLEIANWR NHQETLKYQF DAFYGERSTQ QDIYAGSVQP ILRHLLEGQN
ASVLAYGPTG AGKTHTMLGS PEQPGVIPRA LMDLLQLTRE EGAEGRPWAL SVTMSYLEIY
QEKVLDLLDP ASGDLVIRED CRGNILIPGL SQKPISSFAD FERHFLPASR NRTVGATRLN
QRSSRSHAVL LVKVDQRERL APFRQREGKL YLIDLAGSED NRRTGNKGLR LKESGAINTS
LFVLGKVVDA LNQGLPRVPY RDSKLTRLLQ DSLGGSAHSI LIANIAPERR FYLDTVSALN
FAARSKEVIN RPFTNESLQP HALGPVKLSQ KELLGPPEAK RARGPEEEEI GSPEPMAAPA
SASQKLSPLQ KLSSMDPAML ERLLSLDRLL ASQGSQGAPL LSTPKRERMV LMKTVEEKDL
EIERLKTKQK ELEAKMLAQK AEEKENHCPT MLRPLSHRTV TGAKPLKKAV VMPLQLIQEQ
AASPNAEIHI LKNKGRKRKL ESLDALEPEE KAEDCWELQI SPELLAHGRQ KILDLLNEGS
ARDLRSLQRI GPKKAQLIVG WRELHGPFSQ VEDLERVEGI TGKQMESFLK ANILGLAAGQ
RCGAS
//
ID KIF22_HUMAN Reviewed; 665 AA.
AC Q14807; B2R5M0; B7Z265; O60845; O94814; Q53F58; Q9BT46;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-SEP-2001, sequence version 5.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=Kinesin-like protein KIF22;
DE AltName: Full=Kinesin-like DNA-binding protein;
DE AltName: Full=Kinesin-like protein 4;
GN Name=KIF22; Synonyms=KID, KNSL4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8599929;
RA Tokai N., Fujimoto-Nishiyama A., Toyoshima Y., Yonemura S.,
RA Tsukita S., Inoue J., Yamamoto T.;
RT "Kid, a novel kinesin-like DNA binding protein, is localized to
RT chromosomes and the mitotic spindle.";
RL EMBO J. 15:457-467(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9790757; DOI=10.1006/geno.1998.5452;
RA Song J., Murakami H., Yang Z.Q., Koga C., Adati N., Murata T.,
RA Geltinger C., Saito-Ohara F., Ikeuchi T., Matsumura M., Itakura K.,
RA Kanazawa I., Sun K., Yokoyama K.K.;
RT "Human genes for KNSL4 and MAZ are located close to one another on
RT chromosome 16p11.2.";
RL Genomics 52:374-377(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Adrenal gland, Amygdala, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney epithelium;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R.,
RA Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L.,
RA Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E.,
RA Harris P.C., Venter J.C., Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from
RT human chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP INTERACTION WITH SIAH1, AND DEGRADATION.
RX PubMed=11146551; DOI=10.1038/sj.onc.1204002;
RA Germani A., Bruzzoni-Giovanelli H., Fellous A., Gisselbrecht S.,
RA Varin-Blank N., Calvo F.;
RT "SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by
RT the proteasome pathway during mitosis.";
RL Oncogene 19:5997-6006(2000).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-452, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [12]
RP INTERACTION WITH FAM83D.
RX PubMed=18485706; DOI=10.1016/j.cub.2008.04.041;
RA Santamaria A., Nagel S., Sillje H.H.W., Nigg E.A.;
RT "The spindle protein CHICA mediates localization of the chromokinesin
RT Kid to the mitotic spindle.";
RL Curr. Biol. 18:723-729(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412 AND SER-427, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412 AND SER-427, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412; SER-543; SER-562
RP AND SER-581, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP TISSUE SPECIFICITY, VARIANTS SEMDJL2 SER-148; LEU-148 AND GLN-149, AND
RP VARIANT GLN-232.
RX PubMed=22152677; DOI=10.1016/j.ajhg.2011.10.015;
RA Min B.J., Kim N., Chung T., Kim O.H., Nishimura G., Chung C.Y.,
RA Song H.R., Kim H.W., Lee H.R., Kim J., Kang T.H., Seo M.E., Yang S.D.,
RA Kim D.H., Lee S.B., Kim J.I., Seo J.S., Choi J.Y., Kang D., Kim D.,
RA Park W.Y., Cho T.J.;
RT "Whole-exome sequencing identifies mutations of KIF22 in
RT spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic
RT type.";
RL Am. J. Hum. Genet. 89:760-766(2011).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP STRUCTURE BY NMR OF 570-660.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RSGI RUH-070, a C-terminal domain of kinesin-
RT like protein KIF22 from human.";
RL Submitted (AUG-2007) to the PDB data bank.
RN [20]
RP VARIANTS SEMDJL2 LEU-148; GLN-149 AND LEU-149.
RX PubMed=22152678; DOI=10.1016/j.ajhg.2011.10.016;
RA Boyden E.D., Campos-Xavier A.B., Kalamajski S., Cameron T.L.,
RA Suarez P., Tanackovic G., Andria G., Ballhausen D., Briggs M.D.,
RA Hartley C., Cohn D.H., Davidson H.R., Hall C., Ikegawa S., Jouk P.S.,
RA Konig R., Megarbane A., Nishimura G., Lachman R.S., Mortier G.,
RA Rimoin D.L., Rogers R.C., Rossi M., Sawada H., Scott R., Unger S.,
RA Valadares E.R., Bateman J.F., Warman M.L., Superti-Furga A.,
RA Bonafe L.;
RT "Recurrent dominant mutations affecting two adjacent residues in the
RT motor domain of the monomeric kinesin KIF22 result in skeletal
RT dysplasia and joint laxity.";
RL Am. J. Hum. Genet. 89:767-772(2011).
RN [21]
RP ERRATUM.
RA Boyden E.D., Campos-Xavier A.B., Kalamajski S., Cameron T.L.,
RA Suarez P., Tanackovic G., Andria G., Ballhausen D., Briggs M.D.,
RA Hartley C., Cohn D.H., Davidson H.R., Hall C., Ikegawa S., Jouk P.S.,
RA Konig R., Megarbane A., Nishimura G., Lachman R.S., Mortier G.,
RA Rimoin D.L., Rogers R.C., Rossi M., Sawada H., Scott R., Unger S.,
RA Valadares E.R., Bateman J.F., Warman M.L., Superti-Furga A.,
RA Bonafe L.;
RL Am. J. Hum. Genet. 90:170-170(2012).
CC -!- FUNCTION: Kinesin family that is involved in spindle formation and
CC the movements of chromosomes during mitosis and meiosis. Binds to
CC microtubules and to DNA.
CC -!- SUBUNIT: Interacts with FAM83D.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton (Probable).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14807-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14807-2; Sequence=VSP_046428;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in bone, cartilage, joint capsule,
CC ligament, skin, and primary cultured chondrocytes.
CC -!- PTM: Ubiquitinated; mediated by SIAH1 and leading to its
CC subsequent proteasomal degradation (Probable).
CC -!- DISEASE: Spondyloepimetaphyseal dysplasia with joint laxity, 2
CC (SEMDJL2) [MIM:603546]: A bone disease characterized by short
CC stature, distinctive midface retrusion, progressive knee
CC malalignment (genu valgum and/or varum), generalized ligamentous
CC laxity, and mild spinal deformity. Intellectual development is not
CC impaired. Radiographic characteristics include significantly
CC retarded epiphyseal ossification that evolves into epiphyseal
CC dysplasia and precocious osteoarthritis, metaphyseal
CC irregularities and vertical striations, constricted femoral neck,
CC slender metacarpals and metatarsals, and mild thoracolumbar
CC kyphosis or scoliosis with normal or mild platyspondyly. The most
CC distinctive features for differential diagnosis of SEMDJL2 are the
CC slender metacarpals and phalanges and the progressive degeneration
CC of carpal bones; however, these 2 features are evident only in
CC older children and young adults. The soft consistency of cartilage
CC in the airways leads to laryngotracheomalacia with proneness to
CC respiratory obstruction and inspiratory stridor in infancy and
CC childhood. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the kinesin-like protein family.
CC -!- SIMILARITY: Contains 1 kinesin-motor domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC08709.1; Type=Erroneous gene model prediction;
CC Sequence=EAW80007.1; Type=Erroneous gene model prediction;
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DR EMBL; AB017430; BAA33019.2; -; mRNA.
DR EMBL; AB017335; BAA33063.1; -; Genomic_DNA.
DR EMBL; BT007259; AAP35923.1; -; mRNA.
DR EMBL; AK294380; BAH11751.1; -; mRNA.
DR EMBL; AK312234; BAG35167.1; -; mRNA.
DR EMBL; AK316389; BAH14760.1; -; mRNA.
DR EMBL; AK223431; BAD97151.1; -; mRNA.
DR EMBL; AC002301; AAC08709.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC009133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471238; EAW80005.1; -; Genomic_DNA.
DR EMBL; CH471238; EAW80007.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC004352; AAH04352.1; -; mRNA.
DR EMBL; BC028155; AAH28155.1; -; mRNA.
DR RefSeq; NP_001243198.1; NM_001256269.1.
DR RefSeq; NP_001243199.1; NM_001256270.1.
DR RefSeq; NP_015556.1; NM_007317.2.
DR UniGene; Hs.612151; -.
DR PDB; 2EDU; NMR; -; A=570-660.
DR PDB; 3BFN; X-ray; 2.30 A; A=40-400.
DR PDBsum; 2EDU; -.
DR PDBsum; 3BFN; -.
DR ProteinModelPortal; Q14807; -.
DR SMR; Q14807; 40-369, 570-660.
DR IntAct; Q14807; 6.
DR MINT; MINT-156095; -.
DR STRING; 9606.ENSP00000160827; -.
DR ChEMBL; CHEMBL5470; -.
DR PhosphoSite; Q14807; -.
DR DMDM; 19863381; -.
DR PaxDb; Q14807; -.
DR PRIDE; Q14807; -.
DR DNASU; 3835; -.
DR Ensembl; ENST00000160827; ENSP00000160827; ENSG00000079616.
DR Ensembl; ENST00000400751; ENSP00000383562; ENSG00000079616.
DR Ensembl; ENST00000561482; ENSP00000454957; ENSG00000079616.
DR GeneID; 3835; -.
DR KEGG; hsa:3835; -.
DR UCSC; uc002dts.4; human.
DR CTD; 3835; -.
DR GeneCards; GC16P029802; -.
DR HGNC; HGNC:6391; KIF22.
DR HPA; HPA041076; -.
DR MIM; 603213; gene.
DR MIM; 603546; phenotype.
DR neXtProt; NX_Q14807; -.
DR Orphanet; 93360; Spondyloepimetaphyseal dysplasia with multiple dislocations.
DR PharmGKB; PA30180; -.
DR eggNOG; COG5059; -.
DR HOGENOM; HOG000007569; -.
DR HOVERGEN; HBG052252; -.
DR InParanoid; Q14807; -.
DR KO; K10403; -.
DR OMA; AGQRCGP; -.
DR OrthoDB; EOG7Z69BZ; -.
DR PhylomeDB; Q14807; -.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q14807; -.
DR EvolutionaryTrace; Q14807; -.
DR GeneWiki; KIF22; -.
DR GenomeRNAi; 3835; -.
DR NextBio; 15075; -.
DR PRO; PR:Q14807; -.
DR ArrayExpress; Q14807; -.
DR Bgee; Q14807; -.
DR CleanEx; HS_KIF22; -.
DR Genevestigator; Q14807; -.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0005871; C:kinesin complex; IEA:InterPro.
DR GO; GO:0000776; C:kinetochore; TAS:ProtInc.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005819; C:spindle; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0003777; F:microtubule motor activity; TAS:ProtInc.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0006281; P:DNA repair; IEA:InterPro.
DR GO; GO:0007018; P:microtubule-based movement; TAS:Reactome.
DR GO; GO:0007067; P:mitosis; TAS:ProtInc.
DR Gene3D; 3.40.850.10; -; 1.
DR InterPro; IPR003583; Hlx-hairpin-Hlx_DNA-bd_motif.
DR InterPro; IPR026986; KIF22.
DR InterPro; IPR027640; Kinesin-like_fam.
DR InterPro; IPR019821; Kinesin_motor_CS.
DR InterPro; IPR001752; Kinesin_motor_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR010994; RuvA_2-like.
DR PANTHER; PTHR24115; PTHR24115; 1.
DR PANTHER; PTHR24115:SF171; PTHR24115:SF171; 1.
DR Pfam; PF00225; Kinesin; 1.
DR PRINTS; PR00380; KINESINHEAVY.
DR SMART; SM00278; HhH1; 2.
DR SMART; SM00129; KISc; 1.
DR SUPFAM; SSF47781; SSF47781; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS00411; KINESIN_MOTOR_DOMAIN1; 1.
DR PROSITE; PS50067; KINESIN_MOTOR_DOMAIN2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Coiled coil;
KW Complete proteome; Cytoplasm; Cytoskeleton; Disease mutation;
KW DNA-binding; Dwarfism; Microtubule; Motor protein; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1 665 Kinesin-like protein KIF22.
FT /FTId=PRO_0000125433.
FT DOMAIN 40 299 Kinesin-motor.
FT NP_BIND 127 134 ATP (By similarity).
FT COILED 465 508 Potential.
FT MOD_RES 412 412 Phosphoserine.
FT MOD_RES 427 427 Phosphoserine.
FT MOD_RES 452 452 Phosphoserine.
FT MOD_RES 543 543 Phosphoserine.
FT MOD_RES 562 562 Phosphoserine.
FT MOD_RES 581 581 Phosphoserine.
FT VAR_SEQ 1 68 Missing (in isoform 2).
FT /FTId=VSP_046428.
FT VARIANT 148 148 P -> L (in SEMDJL2; dbSNP:rs193922921).
FT /FTId=VAR_067345.
FT VARIANT 148 148 P -> S (in SEMDJL2; dbSNP:rs193922920).
FT /FTId=VAR_067346.
FT VARIANT 149 149 R -> L (in SEMDJL2).
FT /FTId=VAR_067347.
FT VARIANT 149 149 R -> Q (in SEMDJL2; dbSNP:rs193922922).
FT /FTId=VAR_067348.
FT VARIANT 232 232 R -> Q.
FT /FTId=VAR_067349.
FT CONFLICT 24 24 Missing (in Ref. 2; BAA33063).
FT CONFLICT 122 122 S -> KV (in Ref. 2; BAA33063).
FT CONFLICT 135 169 HTMLGSPEQPGVIPRALMDLLQLTREEGAEGRPWA -> TH
FT AGQPRATWGDPAGSHGPPAAHKGGGCRGPAMG (in Ref.
FT 2).
FT CONFLICT 216 216 S -> N (in Ref. 5; BAD97151).
FT CONFLICT 270 270 L -> P (in Ref. 3; BAG35167).
FT CONFLICT 303 303 V -> A (in Ref. 2; BAA33063).
FT CONFLICT 381 381 H -> R (in Ref. 5; BAD97151).
FT CONFLICT 418 456 APASASQKLSPLQKLSSMDPAMLERLLSLDRLLASQGSQ
FT -> SSSLCLPETQPPTEAKAAWTRPCGAPPQLGPSACLPGE
FT P (in Ref. 2; BAA33063).
FT CONFLICT 505 513 ENHCPTMLR -> RTIVPQCSG (in Ref. 2;
FT BAA33063).
FT STRAND 45 50
FT STRAND 85 89
FT STRAND 91 94
FT HELIX 100 107
FT HELIX 109 111
FT HELIX 112 115
FT TURN 116 118
FT STRAND 121 127
FT HELIX 133 137
FT STRAND 141 144
FT HELIX 146 161
FT STRAND 167 180
FT STRAND 183 189
FT HELIX 218 228
FT HELIX 243 245
FT STRAND 246 260
FT STRAND 265 274
FT HELIX 299 312
FT HELIX 320 322
FT HELIX 324 328
FT TURN 329 331
FT STRAND 332 334
FT STRAND 338 345
FT HELIX 349 351
FT HELIX 352 362
FT STRAND 364 369
FT TURN 577 579
FT HELIX 582 598
FT HELIX 601 606
FT HELIX 612 625
FT HELIX 631 636
FT HELIX 642 658
SQ SEQUENCE 665 AA; 73262 MW; C6C0AC96741DD387 CRC64;
MAAGGSTQQR RREMAAASAA AISGAGRCRL SKIGATRRPP PARVRVAVRL RPFVDGTAGA
SDPPCVRGMD SCSLEIANWR NHQETLKYQF DAFYGERSTQ QDIYAGSVQP ILRHLLEGQN
ASVLAYGPTG AGKTHTMLGS PEQPGVIPRA LMDLLQLTRE EGAEGRPWAL SVTMSYLEIY
QEKVLDLLDP ASGDLVIRED CRGNILIPGL SQKPISSFAD FERHFLPASR NRTVGATRLN
QRSSRSHAVL LVKVDQRERL APFRQREGKL YLIDLAGSED NRRTGNKGLR LKESGAINTS
LFVLGKVVDA LNQGLPRVPY RDSKLTRLLQ DSLGGSAHSI LIANIAPERR FYLDTVSALN
FAARSKEVIN RPFTNESLQP HALGPVKLSQ KELLGPPEAK RARGPEEEEI GSPEPMAAPA
SASQKLSPLQ KLSSMDPAML ERLLSLDRLL ASQGSQGAPL LSTPKRERMV LMKTVEEKDL
EIERLKTKQK ELEAKMLAQK AEEKENHCPT MLRPLSHRTV TGAKPLKKAV VMPLQLIQEQ
AASPNAEIHI LKNKGRKRKL ESLDALEPEE KAEDCWELQI SPELLAHGRQ KILDLLNEGS
ARDLRSLQRI GPKKAQLIVG WRELHGPFSQ VEDLERVEGI TGKQMESFLK ANILGLAAGQ
RCGAS
//
MIM
603213
*RECORD*
*FIELD* NO
603213
*FIELD* TI
*603213 KINESIN FAMILY MEMBER 22; KIF22
;;KINESIN-LIKE 4; KNSL4;;
KINESIN-LIKE DNA-BINDING PROTEIN; KID;;
read moreORIGIN OF PLASMID DNA REPLICATION-BINDING PROTEIN; OBP;;
ORIP-BINDING PROTEIN
*FIELD* TX
CLONING
The forces required for microtubule-based movements are generated by
microtubule-associated motor proteins that include cytoplasmic dynein
and kinesin. See KNSL1 (148760). Some members of the kinesin family,
such as the Drosophila NOD protein, appear to be involved in spindle
formation and function, including chromosome segregation. Tokai et al.
(1996) isolated cDNAs encoding a novel member of the kinesin family. The
predicted 665-amino acid protein was designated KID (kinesin-like
DNA-binding protein). The N-terminal region of KID shares greater than
35% sequence homology with the motor domains of other kinesins. The
C-terminal domain has limited but significant homology to NOD. KID also
contains a putative nuclear localization signal. Northern blot analysis
revealed that the 2.3-kb KID mRNA was expressed in all cancer cell lines
tested and in various somatic tissues. In cancer cells, other faint
bands were also detected.
Zhang and Nonoyama (1994) identified partial cDNAs encoding 2 cellular
proteins that bind to the origin of plasmid DNA replication (oriP) of
Epstein-Barr virus. The 2 proteins, designated OBP1 (oriP-binding
protein 1) and OBP2, appeared to result from differentially spliced
transcripts derived from a single gene.
Using RT-PCR in C57B mice, Min et al. (2011) detected expression of
Kif22 mRNA in bone, cartilage, liver, ovary, small intestine, and
spleen. KIF22 mRNA was detected in bone, cartilage, joint capsule,
ligament, skin, and primary cultured chondrocytes harvested from human
donors.
MAPPING
By fluorescence in situ hybridization, Song et al. (1998) mapped the
KNSL4 gene to 16p11.2, within 1.2 kb of the MAZ (600999) gene.
NOMENCLATURE
Lawrence et al. (2004) presented a standardized kinesin nomenclature
based on 14 family designations. Under this system, KIF22 belongs to the
kinesin-10 family.
GENE FUNCTION
Tokai et al. (1996) demonstrated that KID binds DNA and interacts with
microtubules. The ATP/GTPase activity of KID was stimulated by
microtubules. Immunofluorescence studies showed that KID colocalizes
with mitotic chromosomes and that it is enriched in the kinetochore at
anaphase. The authors concluded that KID may play a role in regulating
the movement of chromosomes along microtubules during mitosis.
At anaphase, the linkage between sister chromatids is dissolved and the
separated sisters move toward opposite poles of the spindle. Funabiki
and Murray (2000) developed a method to purify metaphase and anaphase
chromosomes from frog egg extracts and identified proteins that leave
chromosomes at anaphase using a novel form of expression screening. This
approach identified Xkid, a Xenopus homolog of human KID, as a protein
that is degraded in anaphase by ubiquitin-mediated proteolysis.
Immunodepleting Xkid from egg extracts prevented normal chromosome
alignment on the metaphase spindle. Adding a mild excess of wildtype or
nondegradable Xkid to egg extracts prevented the separated chromosomes
from moving toward the poles. Funabiki and Murray (2000) proposed that
Xkid provides the metaphase force that pushes chromosome arms toward the
equator of the spindle and that its destruction is needed for anaphase
chromosome movement. Similarly, Antonio et al. (2000) showed that Xkid
plays an essential role in metaphase chromosome alignment and in its
maintenance. They proposed that Xkid is responsible for the polar
ejection forces acting on chromosome arms. Their results showed that
these forces are essential to ensure that kinetochores and chromosome
arms align on a narrow equatorial plate during metaphase, a prerequisite
for proper chromosome segregation.
Perez et al. (2002) found that germinal vesicle breakdown and spindle
assembly occurred normally at meiosis I in the absence of Xkid. Instead
of proceeding to meiosis II, however, Xkid-depleted oocytes could not
reactivate Cdc2 (116940) and cyclin B (123836), and they entered an
interphase-like state and underwent DNA replication. Expression of an
Xkid mutant lacking the DNA-binding domain allowed the depleted oocytes
to complete meiotic maturation. Perez et al. (2002) concluded that Xkid
has a role in the meiotic cell cycle that is independent from its role
in metaphase chromosome alignment.
MOLECULAR GENETICS
In affected members of a Korean family segregating autosomal dominant
spondyloepimetaphyseal dysplasia and joint laxity of the Hall, or
leptodactylic, type (SEMDJL2; 603546) and in 4 unrelated Korean
patients, Min et al. (2011) identified heterozygosity for missense
mutations in the KIF22 gene (603213.0001-603213.0003).
Boyden et al. (2011) sequenced exon 4 of the KIF22 gene in 32 patients
with SEMDJL2, including 20 patients from 8 families, and identified
heterozygosity for missense mutations (603213.0002, 603213.0003, or
603213.0004) in all 32 patients. The mutations, which involve highly
conserved residues within the KIF22 motor domain near an ATP-binding
site, were not found in unaffected relatives or in 480 controls of
European descent.
*FIELD* AV
.0001
SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, TYPE 2
KIF22, PRO148SER
In a Korean mother, daughter, and son with spondyloepimetaphyseal
dysplasia with joint laxity type 2 (SEMDJL2; 603546), previously
reported by Kim et al. (2009), Min et al. (2011) identified
heterozygosity for a 442C-T transition in exon 4 of the KIF22 gene,
resulting in a pro148-to-ser (P148S) substitution that was predicted to
interfere with ATP binding. The mutation was not found in unaffected
family members or in 1,010 control chromosomes.
.0002
SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, TYPE 2
KIF22, PRO148LEU
In 2 unrelated Korean girls with spondyloepimetaphyseal dysplasia with
joint laxity type 2 (SEMDJL2; 603546), 1 aged 4 years and 1, who was
previously reported by Kim et al. (2009) ('patient 6'), aged 13 years,
Min et al. (2011) identified heterozygosity for a 443C-T transition in
exon 4 of the KIF22 gene, resulting in a pro148-to-leu (P148L)
substitution that was predicted to interfere with ATP binding. The
mutation was not found in unaffected family members or in 1,010 control
chromosomes.
In 4 affected members of an Italian family and 2 affected members of a
UK family with SEMDJL2, as well as 5 sporadic patients from the US,
Brazil, Germany, Japan, and Italy, respectively, Boyden et al. (2011)
identified heterozygosity for the P148L mutation in the KIF22 gene. The
mutation segregated with disease in each family, and was not found in
480 controls of European descent.
.0003
SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, TYPE 2
KIF22, ARG149GLN
In a 4-year-old Korean boy with spondyloepimetaphyseal dysplasia with
joint laxity type 2 (SEMDJL2; 603546) and an unrelated 12-year-old
Korean girl with SEMDJL2, who was previously reported by Kim et al.
(2009) ('patient 4'), Min et al. (2011) identified heterozygosity for a
446G-A transition in exon 4 of the KIF22 gene, resulting in an
arg149-to-gln (R149Q) substitution that was predicted to interfere with
ATP binding. The mutation was not found in unaffected family members or
in 1,010 control chromosomes.
In 14 affected individuals from 6 families with SEMDJL2, from the US,
UK, Italy, Japan, and Belgium, as well as 6 sporadic patients from the
US, UK, France, Germany, Greece, and Lebanon, Boyden et al. (2011)
identified heterozygosity for the R149Q mutation in the KIF22 gene. The
mutation segregated with disease in each family and was not found in 480
controls of European descent.
.0004
SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, TYPE 2
KIF22, ARG149LEU
In a sporadic patient from the United States with SEMDJL2 (603546),
Boyden et al. (2011) identified heterozygosity for a de novo 446G-T
transversion in exon 4 of the KIF22 gene, resulting in an arg149-to-leu
(R149L) substitution at a highly conserved residue near an ATP binding
site within the motor domain. The mutation was not found in the
unaffected parents or in 480 controls of European descent.
*FIELD* RF
1. Antonio, C.; Ferby, I.; Wilhelm, H.; Jones, M.; Karsenti, E.; Nebreda,
A. R.; Vernos, I.: Xkid, a chromokinesin required for chromosome
alignment on the metaphase plate. Cell 102: 425-435, 2000.
2. Boyden, E. D.; Campos-Xavier, A. B.; Kalamajski, S.; Cameron, T.
L.; Suarez, P.; Tanackovic, G.; Andria, G.; Ballhausen, D.; Briggs,
M. D.; Hartley, C.; Cohn, D. H.; Davidson, H. R.; and 19 others
: Recurrent dominant mutations affecting two adjacent residues in
the motor domain of the monomeric kinesin KIF22 result in skeletal
dysplasia and joint laxity. Am. J. Hum. Genet. 89: 767-772, 2011.
Note: Erratum: Am. J. Hum. Genet. 90: 170 only, 2012.
3. Funabiki, H.; Murray, A. W.: The Xenopus chromokinesin Xkid is
essential for metaphase chromosome alignment and must be degraded
to allow anaphase chromosome movement. Cell 102: 411-424, 2000.
4. Kim, O.-H.; Cho, T.-J.; Song, H.-R.; Chung, C. Y.; Miyagawa, S.-I.;
Nishimura, G.; Superti-Furga, A.; Unger, S.: A distinct form of spondyloepimetaphyseal
dysplasia with joint laxity (SEMDJL)-leptodactylic type: radiological
characteristics in seven new patients. Skeletal Radiol. 38: 803-811,
2009.
5. Lawrence, C. J.; Dawe, R. K.; Christie, K. R.; Cleveland, D. W.;
Dawson, S. C.; Endow, S. A.; Goldstein, L. S. B.; Goodson, H. V.;
Hirokawa, N.; Howard, J.; Malmberg, R. L.; McIntosh, J. R.; and 10
others: A standardized kinesin nomenclature. J. Cell Biol. 167:
19-22, 2004.
6. Min, B.-J.; Kim, N.; Chung, T.; Kim, O.-H.; Nishimura, G.; Chung,
C. Y.; Song, H. R.; Kim. H. W.; Lee, H. R.; Kim, J.; Kang, T.-H.;
Seo, M.-E.; and 10 others: Whole-exome sequencing identifies mutations
of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic
type. Am. J. Hum. Genet. 89: 760-766, 2011.
7. Perez, L. H.; Antonio, C.; Flament, S.; Vernos, I.; Nebreda, A.
R.: Xkid chromokinesin is required for the meiosis I to meiosis II
transition in Xenopus laevis oocytes. Nature Cell Biol. 4: 737-742,
2002.
8. Song, J.; Murakami, H.; Yang, Z. Q.; Koga, C.; Adati, N.; Murata,
T.; Geltinger, C.; Saito-Ohara, F.; Ikeuchi, T.; Matsumura, M.; Itakura,
K.; Kanazawa, I.; Sun, K.; Yokoyama, K. K.: Human genes for KNSL4
and MAZ are located close to one another on chromosome 16p11.2. Genomics 52:
374-377, 1998.
9. Tokai, N.; Fujimoto-Nishiyama, A.; Toyoshima, Y.; Yonemura, S.;
Tsukita, S.; Inoue, J.; Yamamoto, T.: Kid, a novel kinesin-like DNA
binding protein, is localized to chromosomes and the mitotic spindle. EMBO
J. 15: 457-467, 1996.
10. Zhang, S.; Nonoyama, M.: The cellular proteins that bind specifically
to the Epstein-Barr virus origin of plasmid DNA replication belong
to a gene family. Proc. Nat. Acad. Sci. 91: 2843-2847, 1994.
*FIELD* CN
Matthew B. Gross - updated: 06/21/2012
Marla J. F. O'Neill - updated: 1/25/2012
Patricia A. Hartz - updated: 12/16/2002
Stylianos E. Antonarakis - updated: 9/5/2000
Carol A. Bocchini - updated: 11/17/1998
*FIELD* CD
Rebekah S. Rasooly: 10/27/1998
*FIELD* ED
mgross: 06/21/2012
carol: 2/9/2012
terry: 1/25/2012
carol: 1/25/2012
carol: 3/9/2009
mgross: 12/20/2002
mgross: 12/17/2002
terry: 12/16/2002
mgross: 9/5/2000
terry: 11/17/1998
carol: 11/16/1998
alopez: 10/27/1998
*RECORD*
*FIELD* NO
603213
*FIELD* TI
*603213 KINESIN FAMILY MEMBER 22; KIF22
;;KINESIN-LIKE 4; KNSL4;;
KINESIN-LIKE DNA-BINDING PROTEIN; KID;;
read moreORIGIN OF PLASMID DNA REPLICATION-BINDING PROTEIN; OBP;;
ORIP-BINDING PROTEIN
*FIELD* TX
CLONING
The forces required for microtubule-based movements are generated by
microtubule-associated motor proteins that include cytoplasmic dynein
and kinesin. See KNSL1 (148760). Some members of the kinesin family,
such as the Drosophila NOD protein, appear to be involved in spindle
formation and function, including chromosome segregation. Tokai et al.
(1996) isolated cDNAs encoding a novel member of the kinesin family. The
predicted 665-amino acid protein was designated KID (kinesin-like
DNA-binding protein). The N-terminal region of KID shares greater than
35% sequence homology with the motor domains of other kinesins. The
C-terminal domain has limited but significant homology to NOD. KID also
contains a putative nuclear localization signal. Northern blot analysis
revealed that the 2.3-kb KID mRNA was expressed in all cancer cell lines
tested and in various somatic tissues. In cancer cells, other faint
bands were also detected.
Zhang and Nonoyama (1994) identified partial cDNAs encoding 2 cellular
proteins that bind to the origin of plasmid DNA replication (oriP) of
Epstein-Barr virus. The 2 proteins, designated OBP1 (oriP-binding
protein 1) and OBP2, appeared to result from differentially spliced
transcripts derived from a single gene.
Using RT-PCR in C57B mice, Min et al. (2011) detected expression of
Kif22 mRNA in bone, cartilage, liver, ovary, small intestine, and
spleen. KIF22 mRNA was detected in bone, cartilage, joint capsule,
ligament, skin, and primary cultured chondrocytes harvested from human
donors.
MAPPING
By fluorescence in situ hybridization, Song et al. (1998) mapped the
KNSL4 gene to 16p11.2, within 1.2 kb of the MAZ (600999) gene.
NOMENCLATURE
Lawrence et al. (2004) presented a standardized kinesin nomenclature
based on 14 family designations. Under this system, KIF22 belongs to the
kinesin-10 family.
GENE FUNCTION
Tokai et al. (1996) demonstrated that KID binds DNA and interacts with
microtubules. The ATP/GTPase activity of KID was stimulated by
microtubules. Immunofluorescence studies showed that KID colocalizes
with mitotic chromosomes and that it is enriched in the kinetochore at
anaphase. The authors concluded that KID may play a role in regulating
the movement of chromosomes along microtubules during mitosis.
At anaphase, the linkage between sister chromatids is dissolved and the
separated sisters move toward opposite poles of the spindle. Funabiki
and Murray (2000) developed a method to purify metaphase and anaphase
chromosomes from frog egg extracts and identified proteins that leave
chromosomes at anaphase using a novel form of expression screening. This
approach identified Xkid, a Xenopus homolog of human KID, as a protein
that is degraded in anaphase by ubiquitin-mediated proteolysis.
Immunodepleting Xkid from egg extracts prevented normal chromosome
alignment on the metaphase spindle. Adding a mild excess of wildtype or
nondegradable Xkid to egg extracts prevented the separated chromosomes
from moving toward the poles. Funabiki and Murray (2000) proposed that
Xkid provides the metaphase force that pushes chromosome arms toward the
equator of the spindle and that its destruction is needed for anaphase
chromosome movement. Similarly, Antonio et al. (2000) showed that Xkid
plays an essential role in metaphase chromosome alignment and in its
maintenance. They proposed that Xkid is responsible for the polar
ejection forces acting on chromosome arms. Their results showed that
these forces are essential to ensure that kinetochores and chromosome
arms align on a narrow equatorial plate during metaphase, a prerequisite
for proper chromosome segregation.
Perez et al. (2002) found that germinal vesicle breakdown and spindle
assembly occurred normally at meiosis I in the absence of Xkid. Instead
of proceeding to meiosis II, however, Xkid-depleted oocytes could not
reactivate Cdc2 (116940) and cyclin B (123836), and they entered an
interphase-like state and underwent DNA replication. Expression of an
Xkid mutant lacking the DNA-binding domain allowed the depleted oocytes
to complete meiotic maturation. Perez et al. (2002) concluded that Xkid
has a role in the meiotic cell cycle that is independent from its role
in metaphase chromosome alignment.
MOLECULAR GENETICS
In affected members of a Korean family segregating autosomal dominant
spondyloepimetaphyseal dysplasia and joint laxity of the Hall, or
leptodactylic, type (SEMDJL2; 603546) and in 4 unrelated Korean
patients, Min et al. (2011) identified heterozygosity for missense
mutations in the KIF22 gene (603213.0001-603213.0003).
Boyden et al. (2011) sequenced exon 4 of the KIF22 gene in 32 patients
with SEMDJL2, including 20 patients from 8 families, and identified
heterozygosity for missense mutations (603213.0002, 603213.0003, or
603213.0004) in all 32 patients. The mutations, which involve highly
conserved residues within the KIF22 motor domain near an ATP-binding
site, were not found in unaffected relatives or in 480 controls of
European descent.
*FIELD* AV
.0001
SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, TYPE 2
KIF22, PRO148SER
In a Korean mother, daughter, and son with spondyloepimetaphyseal
dysplasia with joint laxity type 2 (SEMDJL2; 603546), previously
reported by Kim et al. (2009), Min et al. (2011) identified
heterozygosity for a 442C-T transition in exon 4 of the KIF22 gene,
resulting in a pro148-to-ser (P148S) substitution that was predicted to
interfere with ATP binding. The mutation was not found in unaffected
family members or in 1,010 control chromosomes.
.0002
SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, TYPE 2
KIF22, PRO148LEU
In 2 unrelated Korean girls with spondyloepimetaphyseal dysplasia with
joint laxity type 2 (SEMDJL2; 603546), 1 aged 4 years and 1, who was
previously reported by Kim et al. (2009) ('patient 6'), aged 13 years,
Min et al. (2011) identified heterozygosity for a 443C-T transition in
exon 4 of the KIF22 gene, resulting in a pro148-to-leu (P148L)
substitution that was predicted to interfere with ATP binding. The
mutation was not found in unaffected family members or in 1,010 control
chromosomes.
In 4 affected members of an Italian family and 2 affected members of a
UK family with SEMDJL2, as well as 5 sporadic patients from the US,
Brazil, Germany, Japan, and Italy, respectively, Boyden et al. (2011)
identified heterozygosity for the P148L mutation in the KIF22 gene. The
mutation segregated with disease in each family, and was not found in
480 controls of European descent.
.0003
SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, TYPE 2
KIF22, ARG149GLN
In a 4-year-old Korean boy with spondyloepimetaphyseal dysplasia with
joint laxity type 2 (SEMDJL2; 603546) and an unrelated 12-year-old
Korean girl with SEMDJL2, who was previously reported by Kim et al.
(2009) ('patient 4'), Min et al. (2011) identified heterozygosity for a
446G-A transition in exon 4 of the KIF22 gene, resulting in an
arg149-to-gln (R149Q) substitution that was predicted to interfere with
ATP binding. The mutation was not found in unaffected family members or
in 1,010 control chromosomes.
In 14 affected individuals from 6 families with SEMDJL2, from the US,
UK, Italy, Japan, and Belgium, as well as 6 sporadic patients from the
US, UK, France, Germany, Greece, and Lebanon, Boyden et al. (2011)
identified heterozygosity for the R149Q mutation in the KIF22 gene. The
mutation segregated with disease in each family and was not found in 480
controls of European descent.
.0004
SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, TYPE 2
KIF22, ARG149LEU
In a sporadic patient from the United States with SEMDJL2 (603546),
Boyden et al. (2011) identified heterozygosity for a de novo 446G-T
transversion in exon 4 of the KIF22 gene, resulting in an arg149-to-leu
(R149L) substitution at a highly conserved residue near an ATP binding
site within the motor domain. The mutation was not found in the
unaffected parents or in 480 controls of European descent.
*FIELD* RF
1. Antonio, C.; Ferby, I.; Wilhelm, H.; Jones, M.; Karsenti, E.; Nebreda,
A. R.; Vernos, I.: Xkid, a chromokinesin required for chromosome
alignment on the metaphase plate. Cell 102: 425-435, 2000.
2. Boyden, E. D.; Campos-Xavier, A. B.; Kalamajski, S.; Cameron, T.
L.; Suarez, P.; Tanackovic, G.; Andria, G.; Ballhausen, D.; Briggs,
M. D.; Hartley, C.; Cohn, D. H.; Davidson, H. R.; and 19 others
: Recurrent dominant mutations affecting two adjacent residues in
the motor domain of the monomeric kinesin KIF22 result in skeletal
dysplasia and joint laxity. Am. J. Hum. Genet. 89: 767-772, 2011.
Note: Erratum: Am. J. Hum. Genet. 90: 170 only, 2012.
3. Funabiki, H.; Murray, A. W.: The Xenopus chromokinesin Xkid is
essential for metaphase chromosome alignment and must be degraded
to allow anaphase chromosome movement. Cell 102: 411-424, 2000.
4. Kim, O.-H.; Cho, T.-J.; Song, H.-R.; Chung, C. Y.; Miyagawa, S.-I.;
Nishimura, G.; Superti-Furga, A.; Unger, S.: A distinct form of spondyloepimetaphyseal
dysplasia with joint laxity (SEMDJL)-leptodactylic type: radiological
characteristics in seven new patients. Skeletal Radiol. 38: 803-811,
2009.
5. Lawrence, C. J.; Dawe, R. K.; Christie, K. R.; Cleveland, D. W.;
Dawson, S. C.; Endow, S. A.; Goldstein, L. S. B.; Goodson, H. V.;
Hirokawa, N.; Howard, J.; Malmberg, R. L.; McIntosh, J. R.; and 10
others: A standardized kinesin nomenclature. J. Cell Biol. 167:
19-22, 2004.
6. Min, B.-J.; Kim, N.; Chung, T.; Kim, O.-H.; Nishimura, G.; Chung,
C. Y.; Song, H. R.; Kim. H. W.; Lee, H. R.; Kim, J.; Kang, T.-H.;
Seo, M.-E.; and 10 others: Whole-exome sequencing identifies mutations
of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic
type. Am. J. Hum. Genet. 89: 760-766, 2011.
7. Perez, L. H.; Antonio, C.; Flament, S.; Vernos, I.; Nebreda, A.
R.: Xkid chromokinesin is required for the meiosis I to meiosis II
transition in Xenopus laevis oocytes. Nature Cell Biol. 4: 737-742,
2002.
8. Song, J.; Murakami, H.; Yang, Z. Q.; Koga, C.; Adati, N.; Murata,
T.; Geltinger, C.; Saito-Ohara, F.; Ikeuchi, T.; Matsumura, M.; Itakura,
K.; Kanazawa, I.; Sun, K.; Yokoyama, K. K.: Human genes for KNSL4
and MAZ are located close to one another on chromosome 16p11.2. Genomics 52:
374-377, 1998.
9. Tokai, N.; Fujimoto-Nishiyama, A.; Toyoshima, Y.; Yonemura, S.;
Tsukita, S.; Inoue, J.; Yamamoto, T.: Kid, a novel kinesin-like DNA
binding protein, is localized to chromosomes and the mitotic spindle. EMBO
J. 15: 457-467, 1996.
10. Zhang, S.; Nonoyama, M.: The cellular proteins that bind specifically
to the Epstein-Barr virus origin of plasmid DNA replication belong
to a gene family. Proc. Nat. Acad. Sci. 91: 2843-2847, 1994.
*FIELD* CN
Matthew B. Gross - updated: 06/21/2012
Marla J. F. O'Neill - updated: 1/25/2012
Patricia A. Hartz - updated: 12/16/2002
Stylianos E. Antonarakis - updated: 9/5/2000
Carol A. Bocchini - updated: 11/17/1998
*FIELD* CD
Rebekah S. Rasooly: 10/27/1998
*FIELD* ED
mgross: 06/21/2012
carol: 2/9/2012
terry: 1/25/2012
carol: 1/25/2012
carol: 3/9/2009
mgross: 12/20/2002
mgross: 12/17/2002
terry: 12/16/2002
mgross: 9/5/2000
terry: 11/17/1998
carol: 11/16/1998
alopez: 10/27/1998
MIM
603546
*RECORD*
*FIELD* NO
603546
*FIELD* TI
#603546 SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY TYPE 2; SEMDJL2
;;SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, HALL TYPE;;
read moreSPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, LEPTODACTYLIC
TYPE;;
SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH MULTIPLE DISLOCATIONS, HALL
TYPE
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
spondyloepimetaphyseal dysplasia with joint laxity-2 (SEMDJL2) is caused
by heterozygous mutation in the KIF22 gene (603213) on chromosome 16p11.
DESCRIPTION
Spondyloepimetaphyseal dysplasia with joint laxity type 2 (SEMDJL2) is
characterized by short stature, distinctive midface retrusion,
progressive knee malalignment (genu valgum and/or varum), generalized
ligamentous laxity, and mild spinal deformity. Intellectual development
is not impaired. Radiographic characteristics include significantly
retarded epiphyseal ossification that evolves into epiphyseal dysplasia
and precocious osteoarthritis, metaphyseal irregularities and vertical
striations, constricted femoral neck, slender metacarpals and
metatarsals, and mild thoracolumbar kyphosis or scoliosis with normal or
mild platyspondyly (summary by Min et al., 2011).
The most distinctive features for differential diagnosis of SEMDJL2 are
the slender metacarpals and phalanges and the progressive degeneration
of carpal bones; however, these 2 features are evident only in older
children and young adults. The soft consistency of cartilage in the
airways leads to laryngotracheomalacia with proneness to respiratory
obstruction and inspiratory stridor in infancy and childhood (summary by
Boyden et al., 2011).
NOMENCLATURE
The International Nosology and Classification of Constitutional Disorder
of Bone initially described two disorders of SEMD with dislocation and
joint laxity: SEMDJL (Beighton type) and SEMD with multiple
dislocations, the Hall or leptodactylic type (Hall et al., 1998).
However, in the 2006 revision of Nosology and Classification of Genetic
Skeletal Disorders, the Nosology Group of the International Skeletal
Dysplasia Society proposed the use of the united term 'joint laxity'
instead of the term 'multiple dislocations' (Superti-Furga et al.,
2007). These included 2 conditions: SEMDJL-Beighton type (designated
SEMDJL1 (271640) in OMIM) and SEMDJL-leptodactylic or Hall type
(designated SEMDJL2 in OMIM).
CLINICAL FEATURES
Hall et al. (1998) described 3 children from unrelated families who
presented in infancy with hip dislocation and joint laxity and developed
progressive deformity, particularly involving the knees, spine, and
hips. Clinically, the facial appearance was normal in 2 of the 3 cases;
in the third case, there was mild midface hypoplasia. Cleft palate and
ocular or auditory abnormalities were not present. Cognitive development
was normal. Height measurements were available for only 1 individual,
who was below the 3rd centile at age 5.5 years. Radiographically, the
epiphyses were small, flattened, irregular, and fragmented. The
metaphyses showed widening, irregularity, and streaky sclerosis. The
dorsal vertebral bodies showed posterior decrease in height with
scalloping of the posterior aspects of the lumbar vertebral bodies,
vertebral endplate irregularity, and progressive chordal narrowing of
the interpedicular distances. Scoliosis was not present at birth, but
developed in the first years of life. Hall et al. (1998) regarded the
hand changes as being particularly characteristic. The metacarpals were
gracile, the phalanges were long and slender with squared ends, and the
distal phalangeal tufts were prominent. Carpal bones were individually
small, irregular, and flattened, and the overall size of the carpals was
reduced. There was gross delay in the appearance of the phalangeal
epiphyses. All 3 cases showed absent or severely delayed ossification of
the patellae.
Hall et al. (1998) noted that 2 cases with virtually identical findings,
one reported by Camera et al. (1994) and one (case 5) by Langer et al.
(1997), had been considered examples of sponastrime dysplasia (271510).
Hall et al. (1998) argued, however, that the striking epiphyseal
changes, specific hand findings, and joint laxity with dislocations, in
addition to narrow interpedicular distances and posterior scalloping of
the vertebrae, allowed differentiation of this condition from
sponastrime dysplasia. Hall et al. (1998) also differentiated this
condition from the form of spondyloepimetaphyseal dysplasia with joint
laxity described by Beighton and Kozlowski (1980) (SEMDJL1; 271640),
since SEMDJL1 is associated with kyphoscoliosis at birth, progressing to
severe deformity and talipes equinovarus, cleft palate, congenital heart
disease, and a specific facial dysmorphism. In addition, the particular
radiographic findings in the spine and hands described by Hall et al.
(1998) are absent in SEMDJL1.
Hall et al. (2002) reported 3 additional patients with
spondyloepimetaphyseal dysplasia with multiple dislocations, including a
father with mild manifestations and his daughter who was severely
affected. All of the patients showed facial dysmorphism with a short,
broad, upturned nose. There were striking epiphyseal and metaphyseal
changes of the long bones and joint laxity with multiple dislocations of
the large joints, which were particularly incapacitating at the knees.
Megarbane et al. (2003) reported a 6-year-old male with congenital hip
dislocation, short stature, macrocephaly, low-set ears, short neck, and
hyperlaxity of the wrists and fingers. A broad thorax and limitation of
extension of the elbow were seen. X-rays showed severe delay of
ossification of the epiphyses and carpal bones and a generalized
osteoporosis. There was thoracic scoliosis, mild changes of vertebral
endplates, right hip dislocation, and subluxation of the elbows. The
epiphyses were small, flattened, and irregular. The femoral neck was
slender with flattened femoral epiphyses. Metaphyses of the knees were
irregular, squared with vertical striations. Tarsal bones were normally
ossified. Delay in early development was noted in this case, as in those
reported by Camera et al. (1994) and Hall et al. (2002). Macrocephaly,
frontal bossing, midface hypoplasia with saddle-nose, low-set ears, and
short neck were thought to be common findings.
Holder-Espinasse et al. (2004) reported a patient with a mild form of
spondyloepimetaphyseal dysplasia with persistent inspiratory stridor
secondary to laryngeal stenosis.
Nishimura et al. (2003) described 4 patients with spondyloepimetaphyseal
dysplasia with multiple dislocations, 2 of whom had previously been
diagnosed with sponastrime dysplasia by Masuno et al. (1996) and
Nishimura et al. (1998). Clinical findings included midface hypoplasia,
micromelic short stature, and generalized joint laxity leading to
thoracolumbar scoliosis and multiple joint subluxations.
Laryngotracheomalacia was present in 2 patients, an increased serum
creatine kinase with transient, mild muscle weakness was noted in
another, and pronounced developmental delay was present in 1 patient.
Radiologic findings included mild platyspondyly and stellar ossification
of the calcaneus (both notable in infancy), narrow interpediculate
distances and posterior scalloping of the lumbar spine, constriction of
the femoral neck, delayed epiphyseal ossification that evolved to
epiphyseal dysplasia and degenerative joint disease, metaphyseal
irregularities and striations, and slender, short tubular bones of the
hands.
Rossi et al. (2005) reported a father and son with the Hall type of
spondyloepimetaphyseal dysplasia with multiple dislocations. The father
had short stature and marked joint laxity, including multiple severe
joint dislocations. The son had a milder phenotype.
Park et al. (2007) reported a mother and son with the Hall type of SEMD.
The son had persistent inspiratory stridor beginning at 4 months of age.
Microlaryngoscopy at 22 months revealed laryngeal stenosis secondary to
failure of abduction of the vocal cords. A tracheostomy was performed to
provide an adequate airway. Park et al. (2007) noted that 5 of the 13
published cases of Hall-type SEMD had upper airway obstruction. They
suggested that this is a clinically important diagnostic feature of the
disorder.
Kim et al. (2009) reported the clinical and radiologic findings in a
Korean mother, daughter, and son with Hall-type SEMDJL and in 3
unrelated Korean patients and 1 Japanese patient. The major clinical
features were short stature, midface hypoplasia, and multiple
dislocations and/or ligamentous laxity of the large joints, particularly
at the knees with genu valgum or varum deformity. One patient had mild
mental retardation. No cleft palate was found, and there were no
neurologic, ophthalmologic, or auditory abnormalities. One patient had
undergone surgical correction of an atrial septal defect, and another
had a tracheostomy for tracheomalacia. The main radiologic features
included small, irregular epiphyses, metaphyseal irregularity with
vertical striations that was a consistent finding at the knees,
constricted femoral necks, delayed ossification of the carpal bones, and
slender metacarpals. Progressive thoracolumbar scoliosis was evident
with aging; however, the vertebral bodies appeared normal in height or
showed mild platyspondyly. Kim et al. (2009) stated that the slender
appearance of the metacarpals ('leptodactyly') is distinctive enough for
a definitive diagnosis.
INHERITANCE
Hall et al. (2002) reported variable intrafamilial expressivity of the
disorder and suggested autosomal dominant inheritance with the majority
of cases being new mutations. Nishimura et al. (2003) and Megarbane et
al. (2003) concurred, noting that all of the other cases had been
sporadic, with no clinical differences between males and females, and
none of the families had been consanguineous. Rossi et al. (2005)
reported father-to-son transmission.
MOLECULAR GENETICS
In affected members of a Korean family and 2 unrelated Korean patients
with Hall-type spondyloepimetaphyseal dysplasia and joint laxity,
previously studied by Kim et al. (2009), as well as 3 additional
unrelated Korean patients, Min et al. (2011) performed exome sequencing
and identified sequence variants in the KIF22 gene (603213) in 7 of the
8 affected individuals. Sanger sequencing confirmed 3 heterozygous
missense mutations in the 7 patients (603213.0001-603213.0003). The
patient in whom no KIF22 mutation was found showed a relatively mild
clinical phenotype, with moderate short stature and equivocal midface
retrusion, suggesting the possibility of genetic heterogeneity.
*FIELD* RF
1. Beighton, P.; Kozlowski, K.: Spondylo-epi-metaphyseal dysplasia
with joint laxity and severe, progressive kyphoscoliosis. Skeletal
Radiol. 5: 205-212, 1980.
2. Boyden, E. D.; Campos-Xavier, A. B.; Kalamajski, S.; Cameron, T.
L.; Suarez, P.; Tanackovic, G.; Andria, G.; Ballhausen, D.; Briggs,
M. D.; Hartley, C.; Cohn, D. H.; Davidson, H. R.; and 19 others
: Recurrent dominant mutations affecting two adjacent residues in
the motor domain of the monomeric kinesin KIF22 result in skeletal
dysplasia and joint laxity. Am. J. Hum. Genet. 89: 767-772, 2011.
Note: Erratum: Am. J. Hum. Genet. 90: 170 only, 2012.
3. Camera, G.; Camera, A.; Pozzolo, S.; Costa, P.: Sponastrime dysplasia:
report on a male patient. Pediat. Radiol. 24: 322-324, 1994.
4. Hall, C. M.; Elcioglu, N. H.; MacDermot, K. D.; Offiah, A. C.;
Winter, R. M.: Spondyloepimetaphyseal dysplasia with multiple dislocations
(Hall type): three further cases and evidence of autosomal dominant
inheritance. (Letter) J. Med. Genet. 39: 666-670, 2002.
5. Hall, C. M.; Elcioglu, N. H.; Shaw, D. G.: A distinct form of
spondyloepimetaphyseal dysplasia with multiple dislocations. J. Med.
Genet. 35: 566-572, 1998.
6. Holder-Espinasse, M.; Fayoux, P.; Morillon, S.; Fourier, C.; Dieux-Coeslier,
A.; Manouvrier-Hanu, S.; Le Merrer, M.; Hall, C. M.: Spondyloepimetaphyseal
dysplasia (Hall type) with laryngeal stenosis: a new diagnostic feature? Clin.
Dysmorph. 13: 133-135, 2004.
7. Kim, O.-H.; Cho, T.-J.; Song, H.-R.; Chung, C. Y.; Miyagawa, S.-I.;
Nishimura, G.; Superti-Furga, A.; Unger, S.: A distinct form of spondyloepimetaphyseal
dysplasia with joint laxity (SEMDJL)-leptodactylic type: radiological
characteristics in seven new patients. Skeletal Radiol. 38: 803-811,
2009.
8. Langer, L. O., Jr.; Beals, R. K.; Scott, C. I., Jr.: Sponastrime
dysplasia: diagnostic criteria based on five new and six previously
published cases. Pediat. Radiol. 27: 409-414, 1997.
9. Masuno, M.; Nishimura, G.; Adachi, M.; Hotsubo, T.; Tachibana,
K.; Makita, Y.; Imaizumi, K.; Kuroki, Y.: SPONASTRIME dysplasia:
report on a female patient with severe skeletal changes. Am. J. Med.
Genet. 66: 429-432, 1996.
10. Megarbane, A.; Ghanem, I.; Le Merrer, M.: Spondyloepimetaphyseal
dysplasia with multiple dislocations, leptodactylic type: report of
a new patient and review of the literature. Am. J. Med. Genet. 122A:
252-256, 2003.
11. Min, B.-J.; Kim, N.; Chung, T.; Kim, O.-H.; Nishimura, G.; Chung,
C. Y.; Song, H. R.; Kim. H. W.; Lee, H. R.; Kim, J.; Kang, T.-H.;
Seo, M.-E.; and 10 others: Whole-exome sequencing identifies mutations
of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic
type. Am. J. Hum. Genet. 89: 760-766, 2011.
12. Nishimura, G.; Honma, T.; Shiihara, T.; Manabe, N.; Nakajima,
E.; Adachi, M.; Mikawa, M.; Fukushima, Y.; Ikegawa, S.: Spondyloepimetaphyseal
dysplasia with joint laxity leptodactylic form: clinical course and
phenotypic variations in four patients. Am. J. Med. Genet. 117A:
147-153, 2003.
13. Nishimura, G.; Mikawa, M.; Fukushima, Y.: Another observation
of Langer-type sponastrime dysplasia variant. (Letter) Am. J. Med.
Genet. 80: 288-290, 1998.
14. Park, S.-M.; Hall, C. M.; Gray, R.; Firth, H. V.: Persistent
upper airway obstruction is a diagnostic feature of spondyloepimetaphyseal
dysplasia with multiple dislocations (Hall type) with further evidence
for dominant inheritance. Am. J. Med. Genet. 143A: 2024-2028, 2007.
15. Rossi, M.; De Brasi, D.; Hall, C. M.; Battagliese, A.; Melis,
D.; Sebastio, G.; Andria, G.: A new familial case of spondylo-epi-metaphyseal
dysplasia with multiple dislocations Hall type (leptodactylic form). Clin.
Dysmorph. 14: 13-18, 2005.
16. Superti-Furga, A.; Unger, S.; the Nosology Group of the International
Skeletal Dysplasia Society: Nosology and classification of genetic
skeletal disorders: 2006 revision. Am. J. Med. Genet. 143A: 1-18,
2007.
*FIELD* CS
INHERITANCE:
Autosomal dominant
GROWTH:
[Height];
Short stature
HEAD AND NECK:
[Face];
Midface hypoplasia
SKELETAL:
Spondyloepimetaphyseal dysplasia;
Joint laxity;
[Spine];
Scoliosis;
Caudal narrowing of interpedicular distances;
Vertebral endplate irregularity;
Posterior vertebral body scalloping;
Sacral spinal dysraphism;
[Pelvis];
Congenital hip dislocation;
Small flattened capital femoral epiphyses;
Narrow femoral necks;
Tapered ischia;
[Limbs];
Large joint dislocations (especially knees);
Small, flattened irregular epiphyses;
Irregular, flared metaphyses with streaky sclerosis;
Radial head dislocation;
Genu valgum;
Severely delayed patellae ossification;
[Hands];
Gracile metacarpals;
Long, slender middle and proximal phalanges;
Broad, square ends of distal phalanges;
Prominent distal phalangeal tufts;
Small carpal bones;
Severe delay in phalangeal epiphyseal bone maturation
SKIN, NAILS, HAIR:
[Skin];
Velvety skin;
Normal wound healing
NEUROLOGIC:
[Central nervous system];
Hypotonia
*FIELD* CD
Kelly A. Przylepa: 2/6/2004
*FIELD* ED
joanna: 02/09/2004
joanna: 2/6/2004
*FIELD* CN
Marla J. F. O'Neill - updated: 1/25/2012
Kelly A. Przylepa - updated: 10/25/2007
Siobhan M. Dolan - updated: 7/7/2005
Deborah L. Stone - updated: 11/15/2004
Siobhan M. Dolan - updated: 7/27/2004
Felicity Collins - updated: 12/10/2003
*FIELD* CD
Michael J. Wright: 2/17/1999
*FIELD* ED
carol: 02/09/2012
terry: 1/25/2012
carol: 1/25/2012
carol: 12/20/2011
carol: 10/25/2007
terry: 3/22/2006
carol: 10/18/2005
carol: 7/7/2005
tkritzer: 11/15/2004
carol: 7/27/2004
mgross: 3/18/2004
carol: 12/10/2003
mgross: 2/22/1999
*RECORD*
*FIELD* NO
603546
*FIELD* TI
#603546 SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY TYPE 2; SEMDJL2
;;SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, HALL TYPE;;
read moreSPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH JOINT LAXITY, LEPTODACTYLIC
TYPE;;
SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH MULTIPLE DISLOCATIONS, HALL
TYPE
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
spondyloepimetaphyseal dysplasia with joint laxity-2 (SEMDJL2) is caused
by heterozygous mutation in the KIF22 gene (603213) on chromosome 16p11.
DESCRIPTION
Spondyloepimetaphyseal dysplasia with joint laxity type 2 (SEMDJL2) is
characterized by short stature, distinctive midface retrusion,
progressive knee malalignment (genu valgum and/or varum), generalized
ligamentous laxity, and mild spinal deformity. Intellectual development
is not impaired. Radiographic characteristics include significantly
retarded epiphyseal ossification that evolves into epiphyseal dysplasia
and precocious osteoarthritis, metaphyseal irregularities and vertical
striations, constricted femoral neck, slender metacarpals and
metatarsals, and mild thoracolumbar kyphosis or scoliosis with normal or
mild platyspondyly (summary by Min et al., 2011).
The most distinctive features for differential diagnosis of SEMDJL2 are
the slender metacarpals and phalanges and the progressive degeneration
of carpal bones; however, these 2 features are evident only in older
children and young adults. The soft consistency of cartilage in the
airways leads to laryngotracheomalacia with proneness to respiratory
obstruction and inspiratory stridor in infancy and childhood (summary by
Boyden et al., 2011).
NOMENCLATURE
The International Nosology and Classification of Constitutional Disorder
of Bone initially described two disorders of SEMD with dislocation and
joint laxity: SEMDJL (Beighton type) and SEMD with multiple
dislocations, the Hall or leptodactylic type (Hall et al., 1998).
However, in the 2006 revision of Nosology and Classification of Genetic
Skeletal Disorders, the Nosology Group of the International Skeletal
Dysplasia Society proposed the use of the united term 'joint laxity'
instead of the term 'multiple dislocations' (Superti-Furga et al.,
2007). These included 2 conditions: SEMDJL-Beighton type (designated
SEMDJL1 (271640) in OMIM) and SEMDJL-leptodactylic or Hall type
(designated SEMDJL2 in OMIM).
CLINICAL FEATURES
Hall et al. (1998) described 3 children from unrelated families who
presented in infancy with hip dislocation and joint laxity and developed
progressive deformity, particularly involving the knees, spine, and
hips. Clinically, the facial appearance was normal in 2 of the 3 cases;
in the third case, there was mild midface hypoplasia. Cleft palate and
ocular or auditory abnormalities were not present. Cognitive development
was normal. Height measurements were available for only 1 individual,
who was below the 3rd centile at age 5.5 years. Radiographically, the
epiphyses were small, flattened, irregular, and fragmented. The
metaphyses showed widening, irregularity, and streaky sclerosis. The
dorsal vertebral bodies showed posterior decrease in height with
scalloping of the posterior aspects of the lumbar vertebral bodies,
vertebral endplate irregularity, and progressive chordal narrowing of
the interpedicular distances. Scoliosis was not present at birth, but
developed in the first years of life. Hall et al. (1998) regarded the
hand changes as being particularly characteristic. The metacarpals were
gracile, the phalanges were long and slender with squared ends, and the
distal phalangeal tufts were prominent. Carpal bones were individually
small, irregular, and flattened, and the overall size of the carpals was
reduced. There was gross delay in the appearance of the phalangeal
epiphyses. All 3 cases showed absent or severely delayed ossification of
the patellae.
Hall et al. (1998) noted that 2 cases with virtually identical findings,
one reported by Camera et al. (1994) and one (case 5) by Langer et al.
(1997), had been considered examples of sponastrime dysplasia (271510).
Hall et al. (1998) argued, however, that the striking epiphyseal
changes, specific hand findings, and joint laxity with dislocations, in
addition to narrow interpedicular distances and posterior scalloping of
the vertebrae, allowed differentiation of this condition from
sponastrime dysplasia. Hall et al. (1998) also differentiated this
condition from the form of spondyloepimetaphyseal dysplasia with joint
laxity described by Beighton and Kozlowski (1980) (SEMDJL1; 271640),
since SEMDJL1 is associated with kyphoscoliosis at birth, progressing to
severe deformity and talipes equinovarus, cleft palate, congenital heart
disease, and a specific facial dysmorphism. In addition, the particular
radiographic findings in the spine and hands described by Hall et al.
(1998) are absent in SEMDJL1.
Hall et al. (2002) reported 3 additional patients with
spondyloepimetaphyseal dysplasia with multiple dislocations, including a
father with mild manifestations and his daughter who was severely
affected. All of the patients showed facial dysmorphism with a short,
broad, upturned nose. There were striking epiphyseal and metaphyseal
changes of the long bones and joint laxity with multiple dislocations of
the large joints, which were particularly incapacitating at the knees.
Megarbane et al. (2003) reported a 6-year-old male with congenital hip
dislocation, short stature, macrocephaly, low-set ears, short neck, and
hyperlaxity of the wrists and fingers. A broad thorax and limitation of
extension of the elbow were seen. X-rays showed severe delay of
ossification of the epiphyses and carpal bones and a generalized
osteoporosis. There was thoracic scoliosis, mild changes of vertebral
endplates, right hip dislocation, and subluxation of the elbows. The
epiphyses were small, flattened, and irregular. The femoral neck was
slender with flattened femoral epiphyses. Metaphyses of the knees were
irregular, squared with vertical striations. Tarsal bones were normally
ossified. Delay in early development was noted in this case, as in those
reported by Camera et al. (1994) and Hall et al. (2002). Macrocephaly,
frontal bossing, midface hypoplasia with saddle-nose, low-set ears, and
short neck were thought to be common findings.
Holder-Espinasse et al. (2004) reported a patient with a mild form of
spondyloepimetaphyseal dysplasia with persistent inspiratory stridor
secondary to laryngeal stenosis.
Nishimura et al. (2003) described 4 patients with spondyloepimetaphyseal
dysplasia with multiple dislocations, 2 of whom had previously been
diagnosed with sponastrime dysplasia by Masuno et al. (1996) and
Nishimura et al. (1998). Clinical findings included midface hypoplasia,
micromelic short stature, and generalized joint laxity leading to
thoracolumbar scoliosis and multiple joint subluxations.
Laryngotracheomalacia was present in 2 patients, an increased serum
creatine kinase with transient, mild muscle weakness was noted in
another, and pronounced developmental delay was present in 1 patient.
Radiologic findings included mild platyspondyly and stellar ossification
of the calcaneus (both notable in infancy), narrow interpediculate
distances and posterior scalloping of the lumbar spine, constriction of
the femoral neck, delayed epiphyseal ossification that evolved to
epiphyseal dysplasia and degenerative joint disease, metaphyseal
irregularities and striations, and slender, short tubular bones of the
hands.
Rossi et al. (2005) reported a father and son with the Hall type of
spondyloepimetaphyseal dysplasia with multiple dislocations. The father
had short stature and marked joint laxity, including multiple severe
joint dislocations. The son had a milder phenotype.
Park et al. (2007) reported a mother and son with the Hall type of SEMD.
The son had persistent inspiratory stridor beginning at 4 months of age.
Microlaryngoscopy at 22 months revealed laryngeal stenosis secondary to
failure of abduction of the vocal cords. A tracheostomy was performed to
provide an adequate airway. Park et al. (2007) noted that 5 of the 13
published cases of Hall-type SEMD had upper airway obstruction. They
suggested that this is a clinically important diagnostic feature of the
disorder.
Kim et al. (2009) reported the clinical and radiologic findings in a
Korean mother, daughter, and son with Hall-type SEMDJL and in 3
unrelated Korean patients and 1 Japanese patient. The major clinical
features were short stature, midface hypoplasia, and multiple
dislocations and/or ligamentous laxity of the large joints, particularly
at the knees with genu valgum or varum deformity. One patient had mild
mental retardation. No cleft palate was found, and there were no
neurologic, ophthalmologic, or auditory abnormalities. One patient had
undergone surgical correction of an atrial septal defect, and another
had a tracheostomy for tracheomalacia. The main radiologic features
included small, irregular epiphyses, metaphyseal irregularity with
vertical striations that was a consistent finding at the knees,
constricted femoral necks, delayed ossification of the carpal bones, and
slender metacarpals. Progressive thoracolumbar scoliosis was evident
with aging; however, the vertebral bodies appeared normal in height or
showed mild platyspondyly. Kim et al. (2009) stated that the slender
appearance of the metacarpals ('leptodactyly') is distinctive enough for
a definitive diagnosis.
INHERITANCE
Hall et al. (2002) reported variable intrafamilial expressivity of the
disorder and suggested autosomal dominant inheritance with the majority
of cases being new mutations. Nishimura et al. (2003) and Megarbane et
al. (2003) concurred, noting that all of the other cases had been
sporadic, with no clinical differences between males and females, and
none of the families had been consanguineous. Rossi et al. (2005)
reported father-to-son transmission.
MOLECULAR GENETICS
In affected members of a Korean family and 2 unrelated Korean patients
with Hall-type spondyloepimetaphyseal dysplasia and joint laxity,
previously studied by Kim et al. (2009), as well as 3 additional
unrelated Korean patients, Min et al. (2011) performed exome sequencing
and identified sequence variants in the KIF22 gene (603213) in 7 of the
8 affected individuals. Sanger sequencing confirmed 3 heterozygous
missense mutations in the 7 patients (603213.0001-603213.0003). The
patient in whom no KIF22 mutation was found showed a relatively mild
clinical phenotype, with moderate short stature and equivocal midface
retrusion, suggesting the possibility of genetic heterogeneity.
*FIELD* RF
1. Beighton, P.; Kozlowski, K.: Spondylo-epi-metaphyseal dysplasia
with joint laxity and severe, progressive kyphoscoliosis. Skeletal
Radiol. 5: 205-212, 1980.
2. Boyden, E. D.; Campos-Xavier, A. B.; Kalamajski, S.; Cameron, T.
L.; Suarez, P.; Tanackovic, G.; Andria, G.; Ballhausen, D.; Briggs,
M. D.; Hartley, C.; Cohn, D. H.; Davidson, H. R.; and 19 others
: Recurrent dominant mutations affecting two adjacent residues in
the motor domain of the monomeric kinesin KIF22 result in skeletal
dysplasia and joint laxity. Am. J. Hum. Genet. 89: 767-772, 2011.
Note: Erratum: Am. J. Hum. Genet. 90: 170 only, 2012.
3. Camera, G.; Camera, A.; Pozzolo, S.; Costa, P.: Sponastrime dysplasia:
report on a male patient. Pediat. Radiol. 24: 322-324, 1994.
4. Hall, C. M.; Elcioglu, N. H.; MacDermot, K. D.; Offiah, A. C.;
Winter, R. M.: Spondyloepimetaphyseal dysplasia with multiple dislocations
(Hall type): three further cases and evidence of autosomal dominant
inheritance. (Letter) J. Med. Genet. 39: 666-670, 2002.
5. Hall, C. M.; Elcioglu, N. H.; Shaw, D. G.: A distinct form of
spondyloepimetaphyseal dysplasia with multiple dislocations. J. Med.
Genet. 35: 566-572, 1998.
6. Holder-Espinasse, M.; Fayoux, P.; Morillon, S.; Fourier, C.; Dieux-Coeslier,
A.; Manouvrier-Hanu, S.; Le Merrer, M.; Hall, C. M.: Spondyloepimetaphyseal
dysplasia (Hall type) with laryngeal stenosis: a new diagnostic feature? Clin.
Dysmorph. 13: 133-135, 2004.
7. Kim, O.-H.; Cho, T.-J.; Song, H.-R.; Chung, C. Y.; Miyagawa, S.-I.;
Nishimura, G.; Superti-Furga, A.; Unger, S.: A distinct form of spondyloepimetaphyseal
dysplasia with joint laxity (SEMDJL)-leptodactylic type: radiological
characteristics in seven new patients. Skeletal Radiol. 38: 803-811,
2009.
8. Langer, L. O., Jr.; Beals, R. K.; Scott, C. I., Jr.: Sponastrime
dysplasia: diagnostic criteria based on five new and six previously
published cases. Pediat. Radiol. 27: 409-414, 1997.
9. Masuno, M.; Nishimura, G.; Adachi, M.; Hotsubo, T.; Tachibana,
K.; Makita, Y.; Imaizumi, K.; Kuroki, Y.: SPONASTRIME dysplasia:
report on a female patient with severe skeletal changes. Am. J. Med.
Genet. 66: 429-432, 1996.
10. Megarbane, A.; Ghanem, I.; Le Merrer, M.: Spondyloepimetaphyseal
dysplasia with multiple dislocations, leptodactylic type: report of
a new patient and review of the literature. Am. J. Med. Genet. 122A:
252-256, 2003.
11. Min, B.-J.; Kim, N.; Chung, T.; Kim, O.-H.; Nishimura, G.; Chung,
C. Y.; Song, H. R.; Kim. H. W.; Lee, H. R.; Kim, J.; Kang, T.-H.;
Seo, M.-E.; and 10 others: Whole-exome sequencing identifies mutations
of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic
type. Am. J. Hum. Genet. 89: 760-766, 2011.
12. Nishimura, G.; Honma, T.; Shiihara, T.; Manabe, N.; Nakajima,
E.; Adachi, M.; Mikawa, M.; Fukushima, Y.; Ikegawa, S.: Spondyloepimetaphyseal
dysplasia with joint laxity leptodactylic form: clinical course and
phenotypic variations in four patients. Am. J. Med. Genet. 117A:
147-153, 2003.
13. Nishimura, G.; Mikawa, M.; Fukushima, Y.: Another observation
of Langer-type sponastrime dysplasia variant. (Letter) Am. J. Med.
Genet. 80: 288-290, 1998.
14. Park, S.-M.; Hall, C. M.; Gray, R.; Firth, H. V.: Persistent
upper airway obstruction is a diagnostic feature of spondyloepimetaphyseal
dysplasia with multiple dislocations (Hall type) with further evidence
for dominant inheritance. Am. J. Med. Genet. 143A: 2024-2028, 2007.
15. Rossi, M.; De Brasi, D.; Hall, C. M.; Battagliese, A.; Melis,
D.; Sebastio, G.; Andria, G.: A new familial case of spondylo-epi-metaphyseal
dysplasia with multiple dislocations Hall type (leptodactylic form). Clin.
Dysmorph. 14: 13-18, 2005.
16. Superti-Furga, A.; Unger, S.; the Nosology Group of the International
Skeletal Dysplasia Society: Nosology and classification of genetic
skeletal disorders: 2006 revision. Am. J. Med. Genet. 143A: 1-18,
2007.
*FIELD* CS
INHERITANCE:
Autosomal dominant
GROWTH:
[Height];
Short stature
HEAD AND NECK:
[Face];
Midface hypoplasia
SKELETAL:
Spondyloepimetaphyseal dysplasia;
Joint laxity;
[Spine];
Scoliosis;
Caudal narrowing of interpedicular distances;
Vertebral endplate irregularity;
Posterior vertebral body scalloping;
Sacral spinal dysraphism;
[Pelvis];
Congenital hip dislocation;
Small flattened capital femoral epiphyses;
Narrow femoral necks;
Tapered ischia;
[Limbs];
Large joint dislocations (especially knees);
Small, flattened irregular epiphyses;
Irregular, flared metaphyses with streaky sclerosis;
Radial head dislocation;
Genu valgum;
Severely delayed patellae ossification;
[Hands];
Gracile metacarpals;
Long, slender middle and proximal phalanges;
Broad, square ends of distal phalanges;
Prominent distal phalangeal tufts;
Small carpal bones;
Severe delay in phalangeal epiphyseal bone maturation
SKIN, NAILS, HAIR:
[Skin];
Velvety skin;
Normal wound healing
NEUROLOGIC:
[Central nervous system];
Hypotonia
*FIELD* CD
Kelly A. Przylepa: 2/6/2004
*FIELD* ED
joanna: 02/09/2004
joanna: 2/6/2004
*FIELD* CN
Marla J. F. O'Neill - updated: 1/25/2012
Kelly A. Przylepa - updated: 10/25/2007
Siobhan M. Dolan - updated: 7/7/2005
Deborah L. Stone - updated: 11/15/2004
Siobhan M. Dolan - updated: 7/27/2004
Felicity Collins - updated: 12/10/2003
*FIELD* CD
Michael J. Wright: 2/17/1999
*FIELD* ED
carol: 02/09/2012
terry: 1/25/2012
carol: 1/25/2012
carol: 12/20/2011
carol: 10/25/2007
terry: 3/22/2006
carol: 10/18/2005
carol: 7/7/2005
tkritzer: 11/15/2004
carol: 7/27/2004
mgross: 3/18/2004
carol: 12/10/2003
mgross: 2/22/1999