Full text data of SERPINH1
SERPINH1
(CBP1, CBP2, HSP47, SERPINH2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Serpin H1 (47 kDa heat shock protein; Arsenic-transactivated protein 3; AsTP3; Cell proliferation-inducing gene 14 protein; Collagen-binding protein; Colligin; Rheumatoid arthritis-related antigen RA-A47; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Serpin H1 (47 kDa heat shock protein; Arsenic-transactivated protein 3; AsTP3; Cell proliferation-inducing gene 14 protein; Collagen-binding protein; Colligin; Rheumatoid arthritis-related antigen RA-A47; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P50454
ID SERPH_HUMAN Reviewed; 418 AA.
AC P50454; B3KVJ3; P29043; Q5XPB4; Q6NSJ6; Q8IY96; Q9NP88;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2002, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Serpin H1;
DE AltName: Full=47 kDa heat shock protein;
DE AltName: Full=Arsenic-transactivated protein 3;
DE Short=AsTP3;
DE AltName: Full=Cell proliferation-inducing gene 14 protein;
DE AltName: Full=Collagen-binding protein;
DE Short=Colligin;
DE AltName: Full=Rheumatoid arthritis-related antigen RA-A47;
DE Flags: Precursor;
GN Name=SERPINH1; Synonyms=CBP1, CBP2, HSP47, SERPINH2; ORFNames=PIG14;
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].
RC TISSUE=Fibroblast;
RX PubMed=1309665; DOI=10.1016/0167-4781(92)90498-O;
RA Clarke E., Sandwal B.D.;
RT "Cloning of a human collagen-binding protein, and its homology with
RT rat gp46, chick hsp47 and mouse J6 proteins.";
RL Biochim. Biophys. Acta 1129:246-248(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7656593;
RA Ikegawa S., Sudo K., Okui K., Nakamura Y.;
RT "Isolation, characterization and chromosomal assignment of human
RT colligin-2 gene (CBP2).";
RL Cytogenet. Cell Genet. 71:182-186(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Cartilage, and Fibroblast;
RX PubMed=11052465; DOI=10.1007/s007740070004;
RA Hattori T., Takahash K., Yutani Y., Fujisawa T., Nakanishi T.,
RA Takigawa M.;
RT "Rheumatoid arthritis-related antigen 47kDa (RA-A47) is a product of
RT colligin-2 and acts as a human HSP47.";
RL J. Bone Miner. Metab. 18:328-334(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wu S.-H., Cheng J., Zheng Y.-J., Zhang Y.-X., Liu Y., Zhong Y.-W.;
RT "Cloning and identification of human AsTP3 gene transactivated by
RT arsenic trioxide in HepG2 cells.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell proliferation gene 14.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [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].
RC TISSUE=Brain, Ovary, and Skin;
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 POLYMORPHISM IN PROMOTER, AND INVOLVEMENT IN PPROM.
RX PubMed=16938879; DOI=10.1073/pnas.0603676103;
RA Wang H., Parry S., Macones G., Sammel M.D., Kuivaniemi H., Tromp G.,
RA Argyropoulos G., Halder I., Shriver M.D., Romero R., Strauss J.F. III;
RT "A functional SNP in the promoter of the SERPINH1 gene increases risk
RT of preterm premature rupture of membranes in African Americans.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:13463-13467(2006).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP VARIANT OI10 PRO-78.
RX PubMed=20188343; DOI=10.1016/j.ajhg.2010.01.034;
RA Christiansen H.E., Schwarze U., Pyott S.M., AlSwaid A., Al Balwi M.,
RA Alrasheed S., Pepin M.G., Weis M.A., Eyre D.R., Byers P.H.;
RT "Homozygosity for a missense mutation in SERPINH1, which encodes the
RT collagen chaperone protein HSP47, results in severe recessive
RT osteogenesis imperfecta.";
RL Am. J. Hum. Genet. 86:389-398(2010).
CC -!- FUNCTION: Binds specifically to collagen. Could be involved as a
CC chaperone in the biosynthetic pathway of collagen.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
CC -!- INDUCTION: By heat shock.
CC -!- POLYMORPHISM: A functional SNP in the promoter of SERPINH1 is
CC associated in African Americans with an increased risk for preterm
CC premature rupture of membranes (PPROM) [MIM:610504]. PPROM is
CC defined as rupture of the membranes before 37 weeks of gestation.
CC SERPINH1 with the -656 T allele displays significantly reduced
CC promoter activity compared to the major -656 C allele. Prematurity
CC is correlated with an increased frequency of the -656 T allele.
CC -!- DISEASE: Osteogenesis imperfecta 10 (OI10) [MIM:613848]: A form of
CC osteogenesis imperfecta, a connective tissue disorder
CC characterized by low bone mass, bone fragility and susceptibility
CC to fractures after minimal trauma. Disease severity ranges from
CC very mild forms without fractures to intrauterine fractures and
CC perinatal lethality. Extraskeletal manifestations, which affect a
CC variable number of patients, are dentinogenesis imperfecta,
CC hearing loss, and blue sclerae. OI10 is an autosomal recessive
CC form characterized by multiple bone deformities and fractures,
CC generalized osteopenia, dentinogenesis imperfecta, and blue
CC sclerae. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the serpin family.
CC -!- WEB RESOURCE: Name=Osteogenesis imperfecta variant database;
CC Note=Serpin H1 (SERPINH1);
CC URL="http://oi.gene.le.ac.uk/home.php?select_db=SERPINH1";
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DR EMBL; X61598; CAA43795.1; -; mRNA.
DR EMBL; D83174; BAA11829.1; -; mRNA.
DR EMBL; AB044778; BAA96788.1; -; mRNA.
DR EMBL; AB044779; BAA96789.1; -; mRNA.
DR EMBL; AY744367; AAU95378.1; -; mRNA.
DR EMBL; AY264853; AAP93914.1; -; mRNA.
DR EMBL; BT007094; AAP35758.1; -; mRNA.
DR EMBL; AK122936; BAG53805.1; -; mRNA.
DR EMBL; CH471076; EAW74974.1; -; Genomic_DNA.
DR EMBL; BC014623; AAH14623.1; -; mRNA.
DR EMBL; BC036298; AAH36298.2; -; mRNA.
DR EMBL; BC070087; AAH70087.1; -; mRNA.
DR PIR; I52968; I52968.
DR PIR; S20608; S20608.
DR RefSeq; NP_001193943.1; NM_001207014.1.
DR RefSeq; NP_001226.2; NM_001235.3.
DR RefSeq; XP_005274427.1; XM_005274370.1.
DR RefSeq; XP_005274428.1; XM_005274371.1.
DR UniGene; Hs.596449; -.
DR ProteinModelPortal; P50454; -.
DR SMR; P50454; 36-418.
DR IntAct; P50454; 14.
DR MINT; MINT-3018432; -.
DR STRING; 9606.ENSP00000350894; -.
DR BindingDB; P50454; -.
DR ChEMBL; CHEMBL5286; -.
DR MEROPS; I04.035; -.
DR PhosphoSite; P50454; -.
DR DMDM; 20141241; -.
DR DOSAC-COBS-2DPAGE; P50454; -.
DR UCD-2DPAGE; P50454; -.
DR PaxDb; P50454; -.
DR PeptideAtlas; P50454; -.
DR PRIDE; P50454; -.
DR DNASU; 871; -.
DR Ensembl; ENST00000358171; ENSP00000350894; ENSG00000149257.
DR Ensembl; ENST00000524558; ENSP00000434412; ENSG00000149257.
DR Ensembl; ENST00000533603; ENSP00000434657; ENSG00000149257.
DR GeneID; 871; -.
DR KEGG; hsa:871; -.
DR UCSC; uc001owr.3; human.
DR CTD; 871; -.
DR GeneCards; GC11P075273; -.
DR HGNC; HGNC:1546; SERPINH1.
DR HPA; CAB004441; -.
DR HPA; HPA029198; -.
DR MIM; 600943; gene.
DR MIM; 610504; phenotype.
DR MIM; 613848; phenotype.
DR neXtProt; NX_P50454; -.
DR Orphanet; 216812; Osteogenesis imperfecta type 3.
DR PharmGKB; PA35034; -.
DR eggNOG; COG4826; -.
DR HOVERGEN; HBG104930; -.
DR InParanoid; P50454; -.
DR KO; K09501; -.
DR OMA; INEWASQ; -.
DR OrthoDB; EOG7GBFX4; -.
DR PhylomeDB; P50454; -.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR ChiTaRS; SERPINH1; human.
DR GeneWiki; Heat_shock_protein_47; -.
DR GenomeRNAi; 871; -.
DR NextBio; 3630; -.
DR PRO; PR:P50454; -.
DR ArrayExpress; P50454; -.
DR Bgee; P50454; -.
DR CleanEx; HS_SERPINH1; -.
DR Genevestigator; P50454; -.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0005518; F:collagen binding; NAS:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:RefGenome.
DR GO; GO:0032964; P:collagen biosynthetic process; IEA:Ensembl.
DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome.
DR GO; GO:0051604; P:protein maturation; IEA:Ensembl.
DR GO; GO:0030162; P:regulation of proteolysis; IBA:RefGenome.
DR GO; GO:0006986; P:response to unfolded protein; TAS:ProtInc.
DR InterPro; IPR023795; Serpin_CS.
DR InterPro; IPR023796; Serpin_dom.
DR InterPro; IPR000215; Serpin_fam.
DR PANTHER; PTHR11461; PTHR11461; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
DR PROSITE; PS00284; SERPIN; 1.
PE 1: Evidence at protein level;
KW Chaperone; Complete proteome; Endoplasmic reticulum; Glycoprotein;
KW Osteogenesis imperfecta; Polymorphism; Reference proteome; Signal;
KW Stress response.
FT SIGNAL 1 18 Potential.
FT CHAIN 19 418 Serpin H1.
FT /FTId=PRO_0000032520.
FT MOTIF 415 418 Prevents secretion from ER (Potential).
FT COMPBIAS 25 29 Poly-Ala.
FT SITE 377 378 Reactive bond homolog (By similarity).
FT CARBOHYD 120 120 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 125 125 N-linked (GlcNAc...) (Potential).
FT VARIANT 41 41 A -> P (in dbSNP:rs7105528).
FT /FTId=VAR_028445.
FT VARIANT 78 78 L -> P (in OI10).
FT /FTId=VAR_063602.
FT CONFLICT 7 10 LSAF -> GTL (in Ref. 1; CAA43795).
FT CONFLICT 14 15 EA -> AV (in Ref. 1; CAA43795).
FT CONFLICT 25 26 AA -> VE (in Ref. 1; CAA43795).
FT CONFLICT 38 38 P -> S (in Ref. 1; CAA43795).
FT CONFLICT 41 41 A -> T (in Ref. 1; CAA43795).
FT CONFLICT 46 48 RSA -> PST (in Ref. 1; CAA43795).
FT CONFLICT 164 164 R -> P (in Ref. 1; CAA43795).
FT CONFLICT 168 169 SA -> RP (in Ref. 2; BAA11829).
FT CONFLICT 235 235 M -> T (in Ref. 1; CAA43795).
FT CONFLICT 255 255 I -> L (in Ref. 1; CAA43795).
FT CONFLICT 270 270 L -> F (in Ref. 9; AAH70087).
FT CONFLICT 409 409 P -> L (in Ref. 1; CAA43795).
SQ SEQUENCE 418 AA; 46441 MW; B7719FCA13A55DEB CRC64;
MRSLLLLSAF CLLEAALAAE VKKPAAAAAP GTAEKLSPKA ATLAERSAGL AFSLYQAMAK
DQAVENILVS PVVVASSLGL VSLGGKATTA SQAKAVLSAE QLRDEEVHAG LGELLRSLSN
STARNVTWKL GSRLYGPSSV SFADDFVRSS KQHYNCEHSK INFRDKRSAL QSINEWAAQT
TDGKLPEVTK DVERTDGALL VNAMFFKPHW DEKFHHKMVD NRGFMVTRSY TVGVMMMHRT
GLYNYYDDEK EKLQIVEMPL AHKLSSLIIL MPHHVEPLER LEKLLTKEQL KIWMGKMQKK
AVAISLPKGV VEVTHDLQKH LAGLGLTEAI DKNKADLSRM SGKKDLYLAS VFHATAFELD
TDGNPFDQDI YGREELRSPK LFYADHPFIF LVRDTQSGSL LFIGRLVRPK GDKMRDEL
//
ID SERPH_HUMAN Reviewed; 418 AA.
AC P50454; B3KVJ3; P29043; Q5XPB4; Q6NSJ6; Q8IY96; Q9NP88;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2002, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Serpin H1;
DE AltName: Full=47 kDa heat shock protein;
DE AltName: Full=Arsenic-transactivated protein 3;
DE Short=AsTP3;
DE AltName: Full=Cell proliferation-inducing gene 14 protein;
DE AltName: Full=Collagen-binding protein;
DE Short=Colligin;
DE AltName: Full=Rheumatoid arthritis-related antigen RA-A47;
DE Flags: Precursor;
GN Name=SERPINH1; Synonyms=CBP1, CBP2, HSP47, SERPINH2; ORFNames=PIG14;
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].
RC TISSUE=Fibroblast;
RX PubMed=1309665; DOI=10.1016/0167-4781(92)90498-O;
RA Clarke E., Sandwal B.D.;
RT "Cloning of a human collagen-binding protein, and its homology with
RT rat gp46, chick hsp47 and mouse J6 proteins.";
RL Biochim. Biophys. Acta 1129:246-248(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7656593;
RA Ikegawa S., Sudo K., Okui K., Nakamura Y.;
RT "Isolation, characterization and chromosomal assignment of human
RT colligin-2 gene (CBP2).";
RL Cytogenet. Cell Genet. 71:182-186(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Cartilage, and Fibroblast;
RX PubMed=11052465; DOI=10.1007/s007740070004;
RA Hattori T., Takahash K., Yutani Y., Fujisawa T., Nakanishi T.,
RA Takigawa M.;
RT "Rheumatoid arthritis-related antigen 47kDa (RA-A47) is a product of
RT colligin-2 and acts as a human HSP47.";
RL J. Bone Miner. Metab. 18:328-334(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wu S.-H., Cheng J., Zheng Y.-J., Zhang Y.-X., Liu Y., Zhong Y.-W.;
RT "Cloning and identification of human AsTP3 gene transactivated by
RT arsenic trioxide in HepG2 cells.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell proliferation gene 14.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [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].
RC TISSUE=Brain, Ovary, and Skin;
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 POLYMORPHISM IN PROMOTER, AND INVOLVEMENT IN PPROM.
RX PubMed=16938879; DOI=10.1073/pnas.0603676103;
RA Wang H., Parry S., Macones G., Sammel M.D., Kuivaniemi H., Tromp G.,
RA Argyropoulos G., Halder I., Shriver M.D., Romero R., Strauss J.F. III;
RT "A functional SNP in the promoter of the SERPINH1 gene increases risk
RT of preterm premature rupture of membranes in African Americans.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:13463-13467(2006).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP VARIANT OI10 PRO-78.
RX PubMed=20188343; DOI=10.1016/j.ajhg.2010.01.034;
RA Christiansen H.E., Schwarze U., Pyott S.M., AlSwaid A., Al Balwi M.,
RA Alrasheed S., Pepin M.G., Weis M.A., Eyre D.R., Byers P.H.;
RT "Homozygosity for a missense mutation in SERPINH1, which encodes the
RT collagen chaperone protein HSP47, results in severe recessive
RT osteogenesis imperfecta.";
RL Am. J. Hum. Genet. 86:389-398(2010).
CC -!- FUNCTION: Binds specifically to collagen. Could be involved as a
CC chaperone in the biosynthetic pathway of collagen.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
CC -!- INDUCTION: By heat shock.
CC -!- POLYMORPHISM: A functional SNP in the promoter of SERPINH1 is
CC associated in African Americans with an increased risk for preterm
CC premature rupture of membranes (PPROM) [MIM:610504]. PPROM is
CC defined as rupture of the membranes before 37 weeks of gestation.
CC SERPINH1 with the -656 T allele displays significantly reduced
CC promoter activity compared to the major -656 C allele. Prematurity
CC is correlated with an increased frequency of the -656 T allele.
CC -!- DISEASE: Osteogenesis imperfecta 10 (OI10) [MIM:613848]: A form of
CC osteogenesis imperfecta, a connective tissue disorder
CC characterized by low bone mass, bone fragility and susceptibility
CC to fractures after minimal trauma. Disease severity ranges from
CC very mild forms without fractures to intrauterine fractures and
CC perinatal lethality. Extraskeletal manifestations, which affect a
CC variable number of patients, are dentinogenesis imperfecta,
CC hearing loss, and blue sclerae. OI10 is an autosomal recessive
CC form characterized by multiple bone deformities and fractures,
CC generalized osteopenia, dentinogenesis imperfecta, and blue
CC sclerae. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the serpin family.
CC -!- WEB RESOURCE: Name=Osteogenesis imperfecta variant database;
CC Note=Serpin H1 (SERPINH1);
CC URL="http://oi.gene.le.ac.uk/home.php?select_db=SERPINH1";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; X61598; CAA43795.1; -; mRNA.
DR EMBL; D83174; BAA11829.1; -; mRNA.
DR EMBL; AB044778; BAA96788.1; -; mRNA.
DR EMBL; AB044779; BAA96789.1; -; mRNA.
DR EMBL; AY744367; AAU95378.1; -; mRNA.
DR EMBL; AY264853; AAP93914.1; -; mRNA.
DR EMBL; BT007094; AAP35758.1; -; mRNA.
DR EMBL; AK122936; BAG53805.1; -; mRNA.
DR EMBL; CH471076; EAW74974.1; -; Genomic_DNA.
DR EMBL; BC014623; AAH14623.1; -; mRNA.
DR EMBL; BC036298; AAH36298.2; -; mRNA.
DR EMBL; BC070087; AAH70087.1; -; mRNA.
DR PIR; I52968; I52968.
DR PIR; S20608; S20608.
DR RefSeq; NP_001193943.1; NM_001207014.1.
DR RefSeq; NP_001226.2; NM_001235.3.
DR RefSeq; XP_005274427.1; XM_005274370.1.
DR RefSeq; XP_005274428.1; XM_005274371.1.
DR UniGene; Hs.596449; -.
DR ProteinModelPortal; P50454; -.
DR SMR; P50454; 36-418.
DR IntAct; P50454; 14.
DR MINT; MINT-3018432; -.
DR STRING; 9606.ENSP00000350894; -.
DR BindingDB; P50454; -.
DR ChEMBL; CHEMBL5286; -.
DR MEROPS; I04.035; -.
DR PhosphoSite; P50454; -.
DR DMDM; 20141241; -.
DR DOSAC-COBS-2DPAGE; P50454; -.
DR UCD-2DPAGE; P50454; -.
DR PaxDb; P50454; -.
DR PeptideAtlas; P50454; -.
DR PRIDE; P50454; -.
DR DNASU; 871; -.
DR Ensembl; ENST00000358171; ENSP00000350894; ENSG00000149257.
DR Ensembl; ENST00000524558; ENSP00000434412; ENSG00000149257.
DR Ensembl; ENST00000533603; ENSP00000434657; ENSG00000149257.
DR GeneID; 871; -.
DR KEGG; hsa:871; -.
DR UCSC; uc001owr.3; human.
DR CTD; 871; -.
DR GeneCards; GC11P075273; -.
DR HGNC; HGNC:1546; SERPINH1.
DR HPA; CAB004441; -.
DR HPA; HPA029198; -.
DR MIM; 600943; gene.
DR MIM; 610504; phenotype.
DR MIM; 613848; phenotype.
DR neXtProt; NX_P50454; -.
DR Orphanet; 216812; Osteogenesis imperfecta type 3.
DR PharmGKB; PA35034; -.
DR eggNOG; COG4826; -.
DR HOVERGEN; HBG104930; -.
DR InParanoid; P50454; -.
DR KO; K09501; -.
DR OMA; INEWASQ; -.
DR OrthoDB; EOG7GBFX4; -.
DR PhylomeDB; P50454; -.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR ChiTaRS; SERPINH1; human.
DR GeneWiki; Heat_shock_protein_47; -.
DR GenomeRNAi; 871; -.
DR NextBio; 3630; -.
DR PRO; PR:P50454; -.
DR ArrayExpress; P50454; -.
DR Bgee; P50454; -.
DR CleanEx; HS_SERPINH1; -.
DR Genevestigator; P50454; -.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0005518; F:collagen binding; NAS:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:RefGenome.
DR GO; GO:0032964; P:collagen biosynthetic process; IEA:Ensembl.
DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome.
DR GO; GO:0051604; P:protein maturation; IEA:Ensembl.
DR GO; GO:0030162; P:regulation of proteolysis; IBA:RefGenome.
DR GO; GO:0006986; P:response to unfolded protein; TAS:ProtInc.
DR InterPro; IPR023795; Serpin_CS.
DR InterPro; IPR023796; Serpin_dom.
DR InterPro; IPR000215; Serpin_fam.
DR PANTHER; PTHR11461; PTHR11461; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
DR PROSITE; PS00284; SERPIN; 1.
PE 1: Evidence at protein level;
KW Chaperone; Complete proteome; Endoplasmic reticulum; Glycoprotein;
KW Osteogenesis imperfecta; Polymorphism; Reference proteome; Signal;
KW Stress response.
FT SIGNAL 1 18 Potential.
FT CHAIN 19 418 Serpin H1.
FT /FTId=PRO_0000032520.
FT MOTIF 415 418 Prevents secretion from ER (Potential).
FT COMPBIAS 25 29 Poly-Ala.
FT SITE 377 378 Reactive bond homolog (By similarity).
FT CARBOHYD 120 120 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 125 125 N-linked (GlcNAc...) (Potential).
FT VARIANT 41 41 A -> P (in dbSNP:rs7105528).
FT /FTId=VAR_028445.
FT VARIANT 78 78 L -> P (in OI10).
FT /FTId=VAR_063602.
FT CONFLICT 7 10 LSAF -> GTL (in Ref. 1; CAA43795).
FT CONFLICT 14 15 EA -> AV (in Ref. 1; CAA43795).
FT CONFLICT 25 26 AA -> VE (in Ref. 1; CAA43795).
FT CONFLICT 38 38 P -> S (in Ref. 1; CAA43795).
FT CONFLICT 41 41 A -> T (in Ref. 1; CAA43795).
FT CONFLICT 46 48 RSA -> PST (in Ref. 1; CAA43795).
FT CONFLICT 164 164 R -> P (in Ref. 1; CAA43795).
FT CONFLICT 168 169 SA -> RP (in Ref. 2; BAA11829).
FT CONFLICT 235 235 M -> T (in Ref. 1; CAA43795).
FT CONFLICT 255 255 I -> L (in Ref. 1; CAA43795).
FT CONFLICT 270 270 L -> F (in Ref. 9; AAH70087).
FT CONFLICT 409 409 P -> L (in Ref. 1; CAA43795).
SQ SEQUENCE 418 AA; 46441 MW; B7719FCA13A55DEB CRC64;
MRSLLLLSAF CLLEAALAAE VKKPAAAAAP GTAEKLSPKA ATLAERSAGL AFSLYQAMAK
DQAVENILVS PVVVASSLGL VSLGGKATTA SQAKAVLSAE QLRDEEVHAG LGELLRSLSN
STARNVTWKL GSRLYGPSSV SFADDFVRSS KQHYNCEHSK INFRDKRSAL QSINEWAAQT
TDGKLPEVTK DVERTDGALL VNAMFFKPHW DEKFHHKMVD NRGFMVTRSY TVGVMMMHRT
GLYNYYDDEK EKLQIVEMPL AHKLSSLIIL MPHHVEPLER LEKLLTKEQL KIWMGKMQKK
AVAISLPKGV VEVTHDLQKH LAGLGLTEAI DKNKADLSRM SGKKDLYLAS VFHATAFELD
TDGNPFDQDI YGREELRSPK LFYADHPFIF LVRDTQSGSL LFIGRLVRPK GDKMRDEL
//
MIM
600943
*RECORD*
*FIELD* NO
600943
*FIELD* TI
*600943 SERPIN PEPTIDASE INHIBITOR, CLADE H, MEMBER 1; SERPINH1
;;COLLAGEN-BINDING PROTEIN 2; CBP2;;
read moreCOLLIGIN 2;;
SERPINH2;;
HEAT-SHOCK PROTEIN 47; HSP47;;
RHEUMATOID ARTHRITIS ANTIGEN-A47; RA-A47
CBP1, INCLUDED
*FIELD* TX
DESCRIPTION
Collagen-binding proteins, or colligins, are glycoproteins that bind
specifically to collagen type I (e.g., 120150, 120160), collagen type IV
(e.g., 120130), and gelatin. Colligins are characterized by an amino
acid structure that includes an N-terminal hydrophobic signal sequence
and 2 putative N-linked oligosaccharide attachment sites (Clarke et al.,
1991). Colligins also have a C-terminal RDEL sequence that acts as an
endoplasmic reticulum (ER) retention sequence. Other features permit the
colligin-binding protein of ER to be classified as a serpin
(serine-arginine protease inhibitor).
CLONING
Ikegawa et al. (1995) isolated and characterized a full-length human
cDNA clone that encodes a 418-amino acid peptide highly homologous (97%
identity) to the human colligin-1 gene (CBP1) reported by Clarke and
Sanwal (1992). Nagai et al. (1999) later found that CBP1 is not
transcribed and represents a pseudogene located on chromosome 9. Ikegawa
et al. (1995) called the novel gene colligin-2 and identified a genomic
clone that contained the entire coding sequence of the cDNA. The authors
found that the colligin-2 gene is expressed ubiquitously among all
normal human tissues except brain and circulating leukocytes.
Nagai et al. (1999) cloned CBP2 from a human skin fibroblast cDNA
library using mouse Hsp47 cDNA as probe. By sequence analysis, they
determined that CBP2 and Hsp47 are identical.
GENE STRUCTURE
Ikegawa and Nakamura (1997) found that the CBP2 gene spans approximately
11 kb of genomic DNA and contains 5 exons.
MAPPING
By fluorescence in situ hybridization Ikegawa et al. (1995) determined
that the CBP2 gene maps to chromosome 11q13.5.
GENE FUNCTION
Ikegawa and Nakamura (1997) noted that the promoter sequence of the
human CBP2 gene shows significant homology to that of its murine
counterpart, which contains several regulatory sequences including
heat-shock and retinoic acid-responsive elements. The findings suggested
that colligin may function as a collagen-specific molecular chaperone
and play a role in the process of retinoic acid-induced differentiation.
Hattori et al. (1998) found that CBP2, synthesized by a chondrocytic
cell line, is recognized as an antigen by sera from rheumatoid arthritis
(RA; 180300) patients. They designated the protein RA-A47 due to its
apparent molecular mass of 47 kD by SDS/PAGE. They also found that
heat-shock treatment or exposure of cells to TGF-beta (see 190180)
enhanced the expression of a 2-kb CBP2 transcript. Tasab et al. (2000)
presented evidence that mammalian CBP2, which they called Hsp47,
preferentially interacted with triple-helical procollagen molecules in
vitro. The association of CBP2 with procollagen coincided with the
formation of a collagen triple helix. Yasuda et al. (2002) found that,
in mice, Kruppel-like factor Zf9 (602053) regulated the transcription of
Cbp2 by binding the BS5-B promoter element in cooperation with Sp2
(601801) and/or Sp3 (601804).
In an individual with a severe deforming form of OI (OI10; 613848),
Christiansen et al. (2010) identified a homozygous mutation in the
SERPINH1 gene (600943.0002) that resulted in degradation of the
endoplasmic reticulum resident HSP47 via proteasome. Type I procollagen
accumulated in the Golgi of fibroblasts from the affected individual and
a population of the secreted type I procollagen was protease sensitive.
Christiansen et al. (2010) suggested that HSP47 monitors the integrity
of the triple helix of type I procollagen at the ER/cis-Golgi boundary
and, when absent, the rate of transit from the ER to the Golgi is
increased and the helical structure is compromised. The normal
3-hydroxylation of the prolyl residue at position 986 of the triple
helical domain of pro-alpha1(I) chains places the role of HSP47
downstream from the CRTAP/P3H1/CyPB complex that is involved in prolyl
3-hydroxylation.
MOLECULAR GENETICS
- Preterm Premature Rupture of the Membranes
In a search for genetic factors contributing to the higher prevalence of
preterm premature rupture of the membranes (PPROM; 610504) in African
American than in European American women, Wang et al. (2006) confirmed a
higher frequency of a -656C-T SNP (600943.0001) in the promoter of the
SERPINH1 gene in African and African American populations than in
European Americans (7.4% versus 4.1%). In 2 case-control studies of
African American neonates from pregnancies complicated by PPROM, the
authors found a significant association between the -656T allele and
PPROM. Wang et al. (2006) noted that SERPINH1 is located on chromosome
11q22.2 at approximately 27 Mb from MMP8 (120355), another gene that has
been associated with PPROM, but stated that they found no evidence for
linkage disequilibrium between the -656C-T SERPINH1 SNP and the
previously studied MMP8 alleles.
- Osteogenesis Imperfecta Type X
Because the SERPINH1 gene encodes a collagen-binding protein that
functions as a chaperone in the endoplasmic reticulum, Christiansen et
al. (2010) screened for mutations in this gene in individuals with OI
whose cells did not produce overmodified type I collagen. In 1
individual, born to clinically normal consanguineous Saudi Arabian
parents, they identified a homozygous missense mutation (600943.0002).
The patient had a severe deforming form of OI, here designated OI type X
(OI10; 613848). The authors stated that the disorder clinically fit into
the OI type III Sillence classification.
ANIMAL MODEL
Nagai et al. (1999) found that Cbp2 knockout was lethal to embryonic
mice.
*FIELD* AV
.0001
PRETERM PREMATURE RUPTURE OF THE MEMBRANES
SERPINH1, -656C-T
In a study of ethnic/racial distribution and a -656C-T SNP in the
promoter of the SERPINH1 gene, Wang et al. (2006) found that the -656T
allele had a greater frequency in African and African American
populations than in European Americans (12.4% versus 4.1%). The -656T
allele displayed significantly reduced promoter activity compared to the
wildtype -656C allele in amnion fibroblasts. Two independent
case-control studies of African American neonates from pregnancies
complicated by preterm premature rupture of the membranes (PPROM;
610504) revealed a significant association between the -656T allele and
PPROM (p less than 0.0009 and 0.0076, respectively); combining the 2
studies (244 cases and 358 controls) resulted in a highly significant
association between the -656T allele and PPROM (p less than 0.0000045).
Wang et al. (2006) stated that this was the first example of an
ancestry-informative marker associated with preterm birth in African
Americans.
.0002
OSTEOGENESIS IMPERFECTA, TYPE X
SERPINH1, LEU78PRO
In a Saudi Arabian patient with osteogenesis imperfecta X (OI10;
613848), Christiansen et al. (2010) identified homozygosity for a 233T-C
transition in the SERPINH1 gene, resulting in a leu78-to-pro (L78P)
substitution. The parents were heterozygous for the mutation. The
patient was the only affected member of the family. The mutation did not
affect posttranslational modification of type I procollagen. It appeared
to accelerate transit of type I procollagen from the ER to the Golgi but
slightly slowed the overall transit time from inside the cell to the
extracellular environment. The overall rate of type I procollagen
production was, however, effectively normal, but the triple helical
conformation of secreted type I collagen was altered so that secreted
type I collagen was protease sensitive at one or more specific sites.
*FIELD* RF
1. Christiansen, H. E.; Schwarze, U.; Pyott, S. M.; AlSwaid, A.; Al
Balwi, M.; Alrasheed, S.; Pepin, M. G.; Weis, M. A.; Eyre, D. R.;
Byers, P. H.: Homozygosity for a missense mutation in SERPINH1, which
encodes the collagen chaperone protein HSP47, results in severe recessive
osteogenesis imperfecta. Am. J. Hum. Genet. 86: 389-398, 2010.
2. Clarke, E. P.; Cates, G. A.; Ball, E. H.; Sanwal, B. D.: A collagen-binding
protein in the endoplasmic reticulum of myoblasts exhibits relationship
with serine protease inhibitors. J. Biol. Chem. 266: 17230-17235,
1991.
3. Clarke, E. P.; Sanwal, B. D.: Cloning of a human collagen-binding
protein, and its homology with rat gp46, chick hsp47 and mouse J6
proteins. Biochim. Biophys. Acta 1129: 246-248, 1992.
4. Hattori, T.; Fujisawa, T.; Sasaki, K.; Yutani, Y.; Nakanishi, T.;
Takahashi, K.; Takigawa, M.: Isolation and characterization of a
rheumatoid arthritis-specific antigen (RA-A47) from a human chondrocytic
cell line (HCS-2/8). Biochem. Biophys. Res. Commun. 245: 679-683,
1998.
5. Ikegawa, S.; Nakamura, Y.: Structure of the gene encoding human
colligin-2 (CBP2). Gene 194: 301-303, 1997.
6. Ikegawa, S.; Sudo, K.; Okui, K.; Nakamura, Y.: Isolation, characterization
and chromosomal assignment of human colligin-2 gene (CBP2). Cytogenet.
Cell Genet. 71: 182-186, 1995.
7. Nagai, N.; Tetuya, Y.; Hosokawa, N.; Nagata, K.: The human genome
has only one functional hsp47 gene (CBP2) and a pseudogene (pshsp47). Gene 227:
241-248, 1999.
8. Tasab, M.; Batten, M. R.; Bulleid, N. J.: Hsp47: a molecular chaperone
that interacts with and stabilizes correctly-folded procollagen. EMBO
J. 19: 2204-2211, 2000.
9. Wang, H.; Parry, S.; Macones, G.; Sammel, M. D.; Kuivaniemi, H.;
Tromp, G.; Argyropoulos, G.; Halder, I.; Shriver, M. D.; Romero, R.;
Strauss, J. F., III: A functional SNP in the promoter of the SERPINH1
gene increases risk of preterm premature rupture of membranes in African
Americans. Proc. Nat. Acad. Sci. 103: 13463-13467, 2006. Note: Erratum:
Proc. Nat. Acad. Sci. 103: 19212 only, 2006.
10. Yasuda, K.; Hirayoshi, K.; Hirata, H.; Kubota, H.; Hosokawa, N.;
Nagata, K.: The Kruppel-like factor Zf9 and proteins in the Sp1 family
regulate the expression of HSP47, a collagen-specific molecular chaperone. J.
Biol. Chem. 277: 44613-44622, 2002.
*FIELD* CN
Nara Sobreira - updated: 3/29/2011
Marla J. F. O'Neill - updated: 10/17/2006
Patricia A. Hartz - updated: 1/16/2003
Victor A. McKusick - updated: 10/31/1997
*FIELD* CD
Victor A. McKusick: 11/13/1995
*FIELD* ED
alopez: 01/30/2013
carol: 3/29/2011
carol: 10/18/2006
terry: 10/17/2006
alopez: 11/14/2003
cwells: 1/22/2003
terry: 1/16/2003
terry: 3/13/2002
dkim: 7/21/1998
psherman: 3/31/1998
terry: 11/7/1997
terry: 10/31/1997
mark: 11/13/1995
*RECORD*
*FIELD* NO
600943
*FIELD* TI
*600943 SERPIN PEPTIDASE INHIBITOR, CLADE H, MEMBER 1; SERPINH1
;;COLLAGEN-BINDING PROTEIN 2; CBP2;;
read moreCOLLIGIN 2;;
SERPINH2;;
HEAT-SHOCK PROTEIN 47; HSP47;;
RHEUMATOID ARTHRITIS ANTIGEN-A47; RA-A47
CBP1, INCLUDED
*FIELD* TX
DESCRIPTION
Collagen-binding proteins, or colligins, are glycoproteins that bind
specifically to collagen type I (e.g., 120150, 120160), collagen type IV
(e.g., 120130), and gelatin. Colligins are characterized by an amino
acid structure that includes an N-terminal hydrophobic signal sequence
and 2 putative N-linked oligosaccharide attachment sites (Clarke et al.,
1991). Colligins also have a C-terminal RDEL sequence that acts as an
endoplasmic reticulum (ER) retention sequence. Other features permit the
colligin-binding protein of ER to be classified as a serpin
(serine-arginine protease inhibitor).
CLONING
Ikegawa et al. (1995) isolated and characterized a full-length human
cDNA clone that encodes a 418-amino acid peptide highly homologous (97%
identity) to the human colligin-1 gene (CBP1) reported by Clarke and
Sanwal (1992). Nagai et al. (1999) later found that CBP1 is not
transcribed and represents a pseudogene located on chromosome 9. Ikegawa
et al. (1995) called the novel gene colligin-2 and identified a genomic
clone that contained the entire coding sequence of the cDNA. The authors
found that the colligin-2 gene is expressed ubiquitously among all
normal human tissues except brain and circulating leukocytes.
Nagai et al. (1999) cloned CBP2 from a human skin fibroblast cDNA
library using mouse Hsp47 cDNA as probe. By sequence analysis, they
determined that CBP2 and Hsp47 are identical.
GENE STRUCTURE
Ikegawa and Nakamura (1997) found that the CBP2 gene spans approximately
11 kb of genomic DNA and contains 5 exons.
MAPPING
By fluorescence in situ hybridization Ikegawa et al. (1995) determined
that the CBP2 gene maps to chromosome 11q13.5.
GENE FUNCTION
Ikegawa and Nakamura (1997) noted that the promoter sequence of the
human CBP2 gene shows significant homology to that of its murine
counterpart, which contains several regulatory sequences including
heat-shock and retinoic acid-responsive elements. The findings suggested
that colligin may function as a collagen-specific molecular chaperone
and play a role in the process of retinoic acid-induced differentiation.
Hattori et al. (1998) found that CBP2, synthesized by a chondrocytic
cell line, is recognized as an antigen by sera from rheumatoid arthritis
(RA; 180300) patients. They designated the protein RA-A47 due to its
apparent molecular mass of 47 kD by SDS/PAGE. They also found that
heat-shock treatment or exposure of cells to TGF-beta (see 190180)
enhanced the expression of a 2-kb CBP2 transcript. Tasab et al. (2000)
presented evidence that mammalian CBP2, which they called Hsp47,
preferentially interacted with triple-helical procollagen molecules in
vitro. The association of CBP2 with procollagen coincided with the
formation of a collagen triple helix. Yasuda et al. (2002) found that,
in mice, Kruppel-like factor Zf9 (602053) regulated the transcription of
Cbp2 by binding the BS5-B promoter element in cooperation with Sp2
(601801) and/or Sp3 (601804).
In an individual with a severe deforming form of OI (OI10; 613848),
Christiansen et al. (2010) identified a homozygous mutation in the
SERPINH1 gene (600943.0002) that resulted in degradation of the
endoplasmic reticulum resident HSP47 via proteasome. Type I procollagen
accumulated in the Golgi of fibroblasts from the affected individual and
a population of the secreted type I procollagen was protease sensitive.
Christiansen et al. (2010) suggested that HSP47 monitors the integrity
of the triple helix of type I procollagen at the ER/cis-Golgi boundary
and, when absent, the rate of transit from the ER to the Golgi is
increased and the helical structure is compromised. The normal
3-hydroxylation of the prolyl residue at position 986 of the triple
helical domain of pro-alpha1(I) chains places the role of HSP47
downstream from the CRTAP/P3H1/CyPB complex that is involved in prolyl
3-hydroxylation.
MOLECULAR GENETICS
- Preterm Premature Rupture of the Membranes
In a search for genetic factors contributing to the higher prevalence of
preterm premature rupture of the membranes (PPROM; 610504) in African
American than in European American women, Wang et al. (2006) confirmed a
higher frequency of a -656C-T SNP (600943.0001) in the promoter of the
SERPINH1 gene in African and African American populations than in
European Americans (7.4% versus 4.1%). In 2 case-control studies of
African American neonates from pregnancies complicated by PPROM, the
authors found a significant association between the -656T allele and
PPROM. Wang et al. (2006) noted that SERPINH1 is located on chromosome
11q22.2 at approximately 27 Mb from MMP8 (120355), another gene that has
been associated with PPROM, but stated that they found no evidence for
linkage disequilibrium between the -656C-T SERPINH1 SNP and the
previously studied MMP8 alleles.
- Osteogenesis Imperfecta Type X
Because the SERPINH1 gene encodes a collagen-binding protein that
functions as a chaperone in the endoplasmic reticulum, Christiansen et
al. (2010) screened for mutations in this gene in individuals with OI
whose cells did not produce overmodified type I collagen. In 1
individual, born to clinically normal consanguineous Saudi Arabian
parents, they identified a homozygous missense mutation (600943.0002).
The patient had a severe deforming form of OI, here designated OI type X
(OI10; 613848). The authors stated that the disorder clinically fit into
the OI type III Sillence classification.
ANIMAL MODEL
Nagai et al. (1999) found that Cbp2 knockout was lethal to embryonic
mice.
*FIELD* AV
.0001
PRETERM PREMATURE RUPTURE OF THE MEMBRANES
SERPINH1, -656C-T
In a study of ethnic/racial distribution and a -656C-T SNP in the
promoter of the SERPINH1 gene, Wang et al. (2006) found that the -656T
allele had a greater frequency in African and African American
populations than in European Americans (12.4% versus 4.1%). The -656T
allele displayed significantly reduced promoter activity compared to the
wildtype -656C allele in amnion fibroblasts. Two independent
case-control studies of African American neonates from pregnancies
complicated by preterm premature rupture of the membranes (PPROM;
610504) revealed a significant association between the -656T allele and
PPROM (p less than 0.0009 and 0.0076, respectively); combining the 2
studies (244 cases and 358 controls) resulted in a highly significant
association between the -656T allele and PPROM (p less than 0.0000045).
Wang et al. (2006) stated that this was the first example of an
ancestry-informative marker associated with preterm birth in African
Americans.
.0002
OSTEOGENESIS IMPERFECTA, TYPE X
SERPINH1, LEU78PRO
In a Saudi Arabian patient with osteogenesis imperfecta X (OI10;
613848), Christiansen et al. (2010) identified homozygosity for a 233T-C
transition in the SERPINH1 gene, resulting in a leu78-to-pro (L78P)
substitution. The parents were heterozygous for the mutation. The
patient was the only affected member of the family. The mutation did not
affect posttranslational modification of type I procollagen. It appeared
to accelerate transit of type I procollagen from the ER to the Golgi but
slightly slowed the overall transit time from inside the cell to the
extracellular environment. The overall rate of type I procollagen
production was, however, effectively normal, but the triple helical
conformation of secreted type I collagen was altered so that secreted
type I collagen was protease sensitive at one or more specific sites.
*FIELD* RF
1. Christiansen, H. E.; Schwarze, U.; Pyott, S. M.; AlSwaid, A.; Al
Balwi, M.; Alrasheed, S.; Pepin, M. G.; Weis, M. A.; Eyre, D. R.;
Byers, P. H.: Homozygosity for a missense mutation in SERPINH1, which
encodes the collagen chaperone protein HSP47, results in severe recessive
osteogenesis imperfecta. Am. J. Hum. Genet. 86: 389-398, 2010.
2. Clarke, E. P.; Cates, G. A.; Ball, E. H.; Sanwal, B. D.: A collagen-binding
protein in the endoplasmic reticulum of myoblasts exhibits relationship
with serine protease inhibitors. J. Biol. Chem. 266: 17230-17235,
1991.
3. Clarke, E. P.; Sanwal, B. D.: Cloning of a human collagen-binding
protein, and its homology with rat gp46, chick hsp47 and mouse J6
proteins. Biochim. Biophys. Acta 1129: 246-248, 1992.
4. Hattori, T.; Fujisawa, T.; Sasaki, K.; Yutani, Y.; Nakanishi, T.;
Takahashi, K.; Takigawa, M.: Isolation and characterization of a
rheumatoid arthritis-specific antigen (RA-A47) from a human chondrocytic
cell line (HCS-2/8). Biochem. Biophys. Res. Commun. 245: 679-683,
1998.
5. Ikegawa, S.; Nakamura, Y.: Structure of the gene encoding human
colligin-2 (CBP2). Gene 194: 301-303, 1997.
6. Ikegawa, S.; Sudo, K.; Okui, K.; Nakamura, Y.: Isolation, characterization
and chromosomal assignment of human colligin-2 gene (CBP2). Cytogenet.
Cell Genet. 71: 182-186, 1995.
7. Nagai, N.; Tetuya, Y.; Hosokawa, N.; Nagata, K.: The human genome
has only one functional hsp47 gene (CBP2) and a pseudogene (pshsp47). Gene 227:
241-248, 1999.
8. Tasab, M.; Batten, M. R.; Bulleid, N. J.: Hsp47: a molecular chaperone
that interacts with and stabilizes correctly-folded procollagen. EMBO
J. 19: 2204-2211, 2000.
9. Wang, H.; Parry, S.; Macones, G.; Sammel, M. D.; Kuivaniemi, H.;
Tromp, G.; Argyropoulos, G.; Halder, I.; Shriver, M. D.; Romero, R.;
Strauss, J. F., III: A functional SNP in the promoter of the SERPINH1
gene increases risk of preterm premature rupture of membranes in African
Americans. Proc. Nat. Acad. Sci. 103: 13463-13467, 2006. Note: Erratum:
Proc. Nat. Acad. Sci. 103: 19212 only, 2006.
10. Yasuda, K.; Hirayoshi, K.; Hirata, H.; Kubota, H.; Hosokawa, N.;
Nagata, K.: The Kruppel-like factor Zf9 and proteins in the Sp1 family
regulate the expression of HSP47, a collagen-specific molecular chaperone. J.
Biol. Chem. 277: 44613-44622, 2002.
*FIELD* CN
Nara Sobreira - updated: 3/29/2011
Marla J. F. O'Neill - updated: 10/17/2006
Patricia A. Hartz - updated: 1/16/2003
Victor A. McKusick - updated: 10/31/1997
*FIELD* CD
Victor A. McKusick: 11/13/1995
*FIELD* ED
alopez: 01/30/2013
carol: 3/29/2011
carol: 10/18/2006
terry: 10/17/2006
alopez: 11/14/2003
cwells: 1/22/2003
terry: 1/16/2003
terry: 3/13/2002
dkim: 7/21/1998
psherman: 3/31/1998
terry: 11/7/1997
terry: 10/31/1997
mark: 11/13/1995
MIM
610504
*RECORD*
*FIELD* NO
610504
*FIELD* TI
#610504 PRETERM PREMATURE RUPTURE OF THE MEMBRANES; PPROM
*FIELD* TX
A number sign (#) is used with this entry because susceptibility to
read morepreterm premature rupture of the membranes (PPROM) has been associated
with polymorphisms in the CBP2 (SERPINH1; 600943), MMP1 (120353), and
MMP8 (120355) genes.
DESCRIPTION
Preterm premature rupture of the membranes is defined as rupture of
membranes before 37 weeks of gestation, which occurs in approximately 3%
of all pregnancies and accounts for about one-third of spontaneous
preterm births (ACOG Practice Bulletin, 1998). Srinivas and Macones
(2005) reviewed the pathophysiology of PPROM and noted that familial
clustering and ethnic differences in the incidence of PPROM suggest
possible genetic influences.
PATHOGENESIS
Maymon et al. (2000) measured levels of MMP1, a key enzyme in the
degradation of interstitial collagens, in amniotic fluid from 353 women,
including those with intact membranes, in term or preterm labor or not
in labor, and those with term and premature rupture of the membranes,
with or without microbial invasion of the amniotic cavity. MMP1 was
detectable in 81.3% (287 of 353) of amniotic fluid samples, and the
concentration increased with increasing gestational age. PPROM was
associated with a significant increase in the median amniotic fluid
concentration of MMP1, both in the presence and absence of infection,
whereas neither term nor preterm parturition was associated with a
significant increase in the concentration of MMP1, with rupture of
membranes at term being associated with a significant decrease in
amniotic fluid MMP1 concentration. Analysis of the matrix
metalloproteinase profile of amniotic fluid in term and preterm rupture
of membranes showed that patterns were similar for every enzyme except
MMP1 and MMP8, suggesting different molecular pathophysiologic
mechanisms for extracellular matrix degradation of rupture of membranes
in term and preterm gestations. Maymon et al. (2000) concluded that MMP1
is implicated in the mechanisms of membrane rupture.
MOLECULAR GENETICS
Fujimoto et al. (2002) analyzed G-1607GG promoter polymorphism in the
MMP1 gene (120353.0001; dbSNP rs1799750) in 75 African American infants
who were born after preterm premature rupture of the membranes (PPROM)
and 235 controls, and found a significant association between fetal
carriage of a 2G allele and PPROM (OR = 2.29; p = 0.028).
In a case-control study of African American neonates and 3 SNPs in the
MMP8 gene (120355.0001), Wang et al. (2004) found a statistically
significant association between the 3-minor-allele haplotype, which
displayed the highest MMP8 promoter activity in trophoblast cells, and
preterm premature rupture of the membranes, with an odds ratio (OR) of
4.63 (p less than 0.0001). Homozygosity for the major allele promoter
haplotype appeared to be protective (OR = 0.52, p less than 0.0002).
In 2 case-control studies of African American neonates from pregnancies
complicated by PPROM and a -656C-T SNP in the promoter of the SERPINH1
gene (600943.0001), Wang et al. (2006) found a significant association
between the -656T allele and PPROM (p less than 0.0000045 for the
combined studies). Wang et al. (2006) noted that SERPINH1 is located on
chromosome 11q22.2 at approximately 27 Mb from the MMP8 gene, which has
also been associated with PPROM, but stated that they found no evidence
for linkage disequilibrium between the -656C-T SERPINH1 SNP and the
previously studied MMP8 alleles.
Wang et al. (2008) identified an MMP1 promoter SNP, 3447T-C (numbering
based on AF007878.1; dbSNP rs2075847) and observed that the minor C
allele was always methylated in vivo; functional studies demonstrated
reduced promoter activity of the C allele. In a case-control study
involving 284 African American neonates from pregnancies complicated by
PPROM and 361 African American neonates from normal term pregnancies,
Wang et al. (2008) found the minor C allele to be protective against
PPROM (OR = 0.7451; p = 0.0326), consistent with its reduced promoter
function. Neonates homozygous for the major T allele had 3.51-higher
risk for PPROM compared to CC homozygotes (p = 0.007). Wang et al.
(2008) concluded that in addition to genetic variation, DNA methylation
plays a role in controlling MMP1 expression and risk of PPROM.
*FIELD* RF
1. ACOG Practice Bulletin: Premature rupture of membranes: clinical
management guidelines for obstetrician-gynecologists. Int. J. Gynec.
Obstet. 63: 75-84, 1998.
2. Fujimoto, T.; Parry, S.; Urbanek, M.; Sammel, M.; Macones, G.;
Kuivaniemi, H.; Romero, R.; Strauss, J. F., III: A single nucleotide
polymorphism in the matrix metalloproteinase-1 (MMP-1) promoter influences
amnion cell MMP-1 expression and risk for preterm premature rupture
of the fetal membranes. J. Biol. Chem. 277: 6296-6302, 2002.
3. Maymon, E.; Romero, R.; Pacora, P.; Gervasi, M.-T.; Bianco, K.;
Ghezzi, F.; Yoon, B. H.: Evidence for the participation of interstitial
collagenase (matrix metalloproteinase 1) in preterm premature rupture
of membranes. Am. J. Obstet. Gynec. 183: 914-920, 2000.
4. Srinivas, S. K.; Macones, G. A.: Preterm premature rupture of
the fetal membranes: current concepts. Minerva Ginecol 57: 389-396,
2005.
5. Wang, H.; Ogawa, M.; Wood, J. R.; Bartolomei, M. S.; Sammel, M.
D.; Kusanovic, J. P.; Walsh, S. W.; Romero, R.; Strauss, J. F., III
: Genetic and epigenetic mechanisms combine to control MMP1 expression
and its association with preterm premature rupture of membranes. Hum.
Molec. Genet. 17: 1087-1096, 2008.
6. Wang, H.; Parry, S.; Macones, G.; Sammel, M. D.; Ferrand, P. E.;
Kuivaniemi, H.; Tromp, G.; Halder, I.; Shriver, M. D.; Romero, R.;
Strauss, J. F., III: Functionally significant SNP MMP8 promoter haplotypes
and preterm premature rupture of membranes (PPROM). Hum. Molec. Genet. 13:
2659-2669, 2004.
7. Wang, H.; Parry, S.; Macones, G.; Sammel, M. D.; Kuivaniemi, H.;
Tromp, G.; Argyropoulos, G.; Halder, I.; Shriver, M. D.; Romero, R.;
Strauss, J. F., III: A functional SNP in the promoter of the SERPINH1
gene increases risk of preterm premature rupture of membranes in African
Americans. Proc. Nat. Acad. Sci. 103: 13463-13467, 2006. Note: Erratum:
Proc. Nat. Acad. Sci. 103: 19212 only, 2006.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/12/2009
Marla J. F. O'Neill - updated: 3/13/2007
*FIELD* CD
Marla J. F. O'Neill: 10/17/2006
*FIELD* ED
alopez: 01/30/2013
wwang: 12/3/2009
terry: 11/12/2009
wwang: 3/14/2007
terry: 3/13/2007
carol: 3/9/2007
carol: 10/18/2006
*RECORD*
*FIELD* NO
610504
*FIELD* TI
#610504 PRETERM PREMATURE RUPTURE OF THE MEMBRANES; PPROM
*FIELD* TX
A number sign (#) is used with this entry because susceptibility to
read morepreterm premature rupture of the membranes (PPROM) has been associated
with polymorphisms in the CBP2 (SERPINH1; 600943), MMP1 (120353), and
MMP8 (120355) genes.
DESCRIPTION
Preterm premature rupture of the membranes is defined as rupture of
membranes before 37 weeks of gestation, which occurs in approximately 3%
of all pregnancies and accounts for about one-third of spontaneous
preterm births (ACOG Practice Bulletin, 1998). Srinivas and Macones
(2005) reviewed the pathophysiology of PPROM and noted that familial
clustering and ethnic differences in the incidence of PPROM suggest
possible genetic influences.
PATHOGENESIS
Maymon et al. (2000) measured levels of MMP1, a key enzyme in the
degradation of interstitial collagens, in amniotic fluid from 353 women,
including those with intact membranes, in term or preterm labor or not
in labor, and those with term and premature rupture of the membranes,
with or without microbial invasion of the amniotic cavity. MMP1 was
detectable in 81.3% (287 of 353) of amniotic fluid samples, and the
concentration increased with increasing gestational age. PPROM was
associated with a significant increase in the median amniotic fluid
concentration of MMP1, both in the presence and absence of infection,
whereas neither term nor preterm parturition was associated with a
significant increase in the concentration of MMP1, with rupture of
membranes at term being associated with a significant decrease in
amniotic fluid MMP1 concentration. Analysis of the matrix
metalloproteinase profile of amniotic fluid in term and preterm rupture
of membranes showed that patterns were similar for every enzyme except
MMP1 and MMP8, suggesting different molecular pathophysiologic
mechanisms for extracellular matrix degradation of rupture of membranes
in term and preterm gestations. Maymon et al. (2000) concluded that MMP1
is implicated in the mechanisms of membrane rupture.
MOLECULAR GENETICS
Fujimoto et al. (2002) analyzed G-1607GG promoter polymorphism in the
MMP1 gene (120353.0001; dbSNP rs1799750) in 75 African American infants
who were born after preterm premature rupture of the membranes (PPROM)
and 235 controls, and found a significant association between fetal
carriage of a 2G allele and PPROM (OR = 2.29; p = 0.028).
In a case-control study of African American neonates and 3 SNPs in the
MMP8 gene (120355.0001), Wang et al. (2004) found a statistically
significant association between the 3-minor-allele haplotype, which
displayed the highest MMP8 promoter activity in trophoblast cells, and
preterm premature rupture of the membranes, with an odds ratio (OR) of
4.63 (p less than 0.0001). Homozygosity for the major allele promoter
haplotype appeared to be protective (OR = 0.52, p less than 0.0002).
In 2 case-control studies of African American neonates from pregnancies
complicated by PPROM and a -656C-T SNP in the promoter of the SERPINH1
gene (600943.0001), Wang et al. (2006) found a significant association
between the -656T allele and PPROM (p less than 0.0000045 for the
combined studies). Wang et al. (2006) noted that SERPINH1 is located on
chromosome 11q22.2 at approximately 27 Mb from the MMP8 gene, which has
also been associated with PPROM, but stated that they found no evidence
for linkage disequilibrium between the -656C-T SERPINH1 SNP and the
previously studied MMP8 alleles.
Wang et al. (2008) identified an MMP1 promoter SNP, 3447T-C (numbering
based on AF007878.1; dbSNP rs2075847) and observed that the minor C
allele was always methylated in vivo; functional studies demonstrated
reduced promoter activity of the C allele. In a case-control study
involving 284 African American neonates from pregnancies complicated by
PPROM and 361 African American neonates from normal term pregnancies,
Wang et al. (2008) found the minor C allele to be protective against
PPROM (OR = 0.7451; p = 0.0326), consistent with its reduced promoter
function. Neonates homozygous for the major T allele had 3.51-higher
risk for PPROM compared to CC homozygotes (p = 0.007). Wang et al.
(2008) concluded that in addition to genetic variation, DNA methylation
plays a role in controlling MMP1 expression and risk of PPROM.
*FIELD* RF
1. ACOG Practice Bulletin: Premature rupture of membranes: clinical
management guidelines for obstetrician-gynecologists. Int. J. Gynec.
Obstet. 63: 75-84, 1998.
2. Fujimoto, T.; Parry, S.; Urbanek, M.; Sammel, M.; Macones, G.;
Kuivaniemi, H.; Romero, R.; Strauss, J. F., III: A single nucleotide
polymorphism in the matrix metalloproteinase-1 (MMP-1) promoter influences
amnion cell MMP-1 expression and risk for preterm premature rupture
of the fetal membranes. J. Biol. Chem. 277: 6296-6302, 2002.
3. Maymon, E.; Romero, R.; Pacora, P.; Gervasi, M.-T.; Bianco, K.;
Ghezzi, F.; Yoon, B. H.: Evidence for the participation of interstitial
collagenase (matrix metalloproteinase 1) in preterm premature rupture
of membranes. Am. J. Obstet. Gynec. 183: 914-920, 2000.
4. Srinivas, S. K.; Macones, G. A.: Preterm premature rupture of
the fetal membranes: current concepts. Minerva Ginecol 57: 389-396,
2005.
5. Wang, H.; Ogawa, M.; Wood, J. R.; Bartolomei, M. S.; Sammel, M.
D.; Kusanovic, J. P.; Walsh, S. W.; Romero, R.; Strauss, J. F., III
: Genetic and epigenetic mechanisms combine to control MMP1 expression
and its association with preterm premature rupture of membranes. Hum.
Molec. Genet. 17: 1087-1096, 2008.
6. Wang, H.; Parry, S.; Macones, G.; Sammel, M. D.; Ferrand, P. E.;
Kuivaniemi, H.; Tromp, G.; Halder, I.; Shriver, M. D.; Romero, R.;
Strauss, J. F., III: Functionally significant SNP MMP8 promoter haplotypes
and preterm premature rupture of membranes (PPROM). Hum. Molec. Genet. 13:
2659-2669, 2004.
7. Wang, H.; Parry, S.; Macones, G.; Sammel, M. D.; Kuivaniemi, H.;
Tromp, G.; Argyropoulos, G.; Halder, I.; Shriver, M. D.; Romero, R.;
Strauss, J. F., III: A functional SNP in the promoter of the SERPINH1
gene increases risk of preterm premature rupture of membranes in African
Americans. Proc. Nat. Acad. Sci. 103: 13463-13467, 2006. Note: Erratum:
Proc. Nat. Acad. Sci. 103: 19212 only, 2006.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/12/2009
Marla J. F. O'Neill - updated: 3/13/2007
*FIELD* CD
Marla J. F. O'Neill: 10/17/2006
*FIELD* ED
alopez: 01/30/2013
wwang: 12/3/2009
terry: 11/12/2009
wwang: 3/14/2007
terry: 3/13/2007
carol: 3/9/2007
carol: 10/18/2006
MIM
613848
*RECORD*
*FIELD* NO
613848
*FIELD* TI
#613848 OSTEOGENESIS IMPERFECTA, TYPE X
;;OI, TYPE X; OI10
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moreosteogenesis imperfecta X can be caused by homozygous mutation in the
SERPINH gene (600943) on chromosome 11q13.5.
DESCRIPTION
Osteogenesis imperfecta (OI) comprises a group of connective tissue
disorders characterized by bone fragility and low bone mass. The
disorder is clinically and genetically heterogeneous. OI type X is an
autosomal recessive form characterized by multiple bone deformities and
fractures, generalized osteopenia, dentinogenesis imperfecta, and blue
sclera (Christiansen et al., 2010).
CLINICAL FEATURES
Christiansen et al. (2010) reported a child with a severe deforming form
of OI who was born to a clinically normal consanguineous Saudi Arabian
couple and was the only affected member in the extended family. At birth
he was noted to have a triangular face, relative macrocephaly,
bitemporal narrowing, blue sclerae, micrognathia, and relatively short
limbs with bowing at the thighs. Radiographs of the chest showed thin
ribs with healing fractures, a fracture of the right humerus, a healing
fracture of the left humerus, and platyspondyly. A skeletal survey at
the age of 1 month was consistent with the diagnosis of osteogenesis
imperfecta. There were multiple bone deformities and fractures that
involved the upper and lower extremities and ribs and generalized
osteopenia. When he was 1 year old, bilateral renal stones were noticed
with left pelviuretic junction obstruction that ultimately required left
nephrectomy because of hydronephrosis and loss of renal function. He had
chronic lung disease of unclear etiology and from the age of 1.5 years
he required continuous oxygen by nasal cannula to maintain adequate
oxygenation. He had small opalescent teeth consistent with
dentinogenesis imperfecta. At age 3 years and 6 months he had sudden
unexplained respiratory distress at home and died soon after arrival at
the hospital. No autopsy was performed.
MOLECULAR GENETICS
Because the SERPINH1 gene encodes a collagen-binding protein that
functions as a chaperone in the endoplasmic reticulum, Christiansen et
al. (2010) screened for mutations in this gene in individuals with OI
whose cells did not produce overmodified type I collagen. In a Saudi
Arabian patient with severe deforming OI X, they identified a homozygous
missense mutation (600943.0002).
*FIELD* RF
1. Christiansen, H. E.; Schwarze, U.; Pyott, S. M.; AlSwaid, A.; Al
Balwi, M.; Alrasheed, S.; Pepin, M. G.; Weis, M. A.; Eyre, D. R.;
Byers, P. H.: Homozygosity for a missense mutation in SERPINH1, which
encodes the collagen chaperone protein HSP47, results in severe recessive
osteogenesis imperfecta. Am. J. Hum. Genet. 86: 389-398, 2010.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature;
[Weight];
Weight less than 5th centile
HEAD AND NECK:
[Head];
Macrocephaly, relative;
Bitemporal narrowing;
Open anterior fontanel;
High forehead;
Prominent forehead;
[Face];
Triangular face;
Midface hypoplasia;
[Eyes];
Blue sclera;
Shallow orbits;
[Mouth];
Micrognathia;
[Teeth];
Dentinogenesis imperfecta
RESPIRATORY:
[Lung];
Chronic lung disease
CHEST:
[External features];
Narrow chest;
[Ribs, sternum, clavicles, and scapulae];
Thin ribs;
Broad ribs
ABDOMEN:
[Gastrointestinal];
Pyloric stenosis
GENITOURINARY:
[Internal genitalia, male];
Inguinal hernia, bilateral;
[Kidneys];
Renal stones, bilateral
SKELETAL:
Bone fractures, multiple;
Osteopenia, generalized;
Bone deformities, multiple;
[Spine];
Platyspondyly;
Scoliosis;
[Limbs];
Short limbs, relative;
Bowing of long bones;
Genu valgum;
Joint laxity, generalized
NEUROLOGIC:
[Central nervous system];
Hypotonia, generalized
VOICE:
High-pitched voice
MOLECULAR BASIS:
Caused by mutation in the serpin peptidase inhibitor, clade H, member
1 (SERPINH1, 600943.0002)
*FIELD* CD
Nara Sobreira: 5/17/2011
*FIELD* ED
joanna: 05/17/2011
joanna: 5/17/2011
*FIELD* CD
Nara Sobreira: 3/29/2011
*FIELD* ED
carol: 05/16/2011
carol: 3/29/2011
*RECORD*
*FIELD* NO
613848
*FIELD* TI
#613848 OSTEOGENESIS IMPERFECTA, TYPE X
;;OI, TYPE X; OI10
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moreosteogenesis imperfecta X can be caused by homozygous mutation in the
SERPINH gene (600943) on chromosome 11q13.5.
DESCRIPTION
Osteogenesis imperfecta (OI) comprises a group of connective tissue
disorders characterized by bone fragility and low bone mass. The
disorder is clinically and genetically heterogeneous. OI type X is an
autosomal recessive form characterized by multiple bone deformities and
fractures, generalized osteopenia, dentinogenesis imperfecta, and blue
sclera (Christiansen et al., 2010).
CLINICAL FEATURES
Christiansen et al. (2010) reported a child with a severe deforming form
of OI who was born to a clinically normal consanguineous Saudi Arabian
couple and was the only affected member in the extended family. At birth
he was noted to have a triangular face, relative macrocephaly,
bitemporal narrowing, blue sclerae, micrognathia, and relatively short
limbs with bowing at the thighs. Radiographs of the chest showed thin
ribs with healing fractures, a fracture of the right humerus, a healing
fracture of the left humerus, and platyspondyly. A skeletal survey at
the age of 1 month was consistent with the diagnosis of osteogenesis
imperfecta. There were multiple bone deformities and fractures that
involved the upper and lower extremities and ribs and generalized
osteopenia. When he was 1 year old, bilateral renal stones were noticed
with left pelviuretic junction obstruction that ultimately required left
nephrectomy because of hydronephrosis and loss of renal function. He had
chronic lung disease of unclear etiology and from the age of 1.5 years
he required continuous oxygen by nasal cannula to maintain adequate
oxygenation. He had small opalescent teeth consistent with
dentinogenesis imperfecta. At age 3 years and 6 months he had sudden
unexplained respiratory distress at home and died soon after arrival at
the hospital. No autopsy was performed.
MOLECULAR GENETICS
Because the SERPINH1 gene encodes a collagen-binding protein that
functions as a chaperone in the endoplasmic reticulum, Christiansen et
al. (2010) screened for mutations in this gene in individuals with OI
whose cells did not produce overmodified type I collagen. In a Saudi
Arabian patient with severe deforming OI X, they identified a homozygous
missense mutation (600943.0002).
*FIELD* RF
1. Christiansen, H. E.; Schwarze, U.; Pyott, S. M.; AlSwaid, A.; Al
Balwi, M.; Alrasheed, S.; Pepin, M. G.; Weis, M. A.; Eyre, D. R.;
Byers, P. H.: Homozygosity for a missense mutation in SERPINH1, which
encodes the collagen chaperone protein HSP47, results in severe recessive
osteogenesis imperfecta. Am. J. Hum. Genet. 86: 389-398, 2010.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature;
[Weight];
Weight less than 5th centile
HEAD AND NECK:
[Head];
Macrocephaly, relative;
Bitemporal narrowing;
Open anterior fontanel;
High forehead;
Prominent forehead;
[Face];
Triangular face;
Midface hypoplasia;
[Eyes];
Blue sclera;
Shallow orbits;
[Mouth];
Micrognathia;
[Teeth];
Dentinogenesis imperfecta
RESPIRATORY:
[Lung];
Chronic lung disease
CHEST:
[External features];
Narrow chest;
[Ribs, sternum, clavicles, and scapulae];
Thin ribs;
Broad ribs
ABDOMEN:
[Gastrointestinal];
Pyloric stenosis
GENITOURINARY:
[Internal genitalia, male];
Inguinal hernia, bilateral;
[Kidneys];
Renal stones, bilateral
SKELETAL:
Bone fractures, multiple;
Osteopenia, generalized;
Bone deformities, multiple;
[Spine];
Platyspondyly;
Scoliosis;
[Limbs];
Short limbs, relative;
Bowing of long bones;
Genu valgum;
Joint laxity, generalized
NEUROLOGIC:
[Central nervous system];
Hypotonia, generalized
VOICE:
High-pitched voice
MOLECULAR BASIS:
Caused by mutation in the serpin peptidase inhibitor, clade H, member
1 (SERPINH1, 600943.0002)
*FIELD* CD
Nara Sobreira: 5/17/2011
*FIELD* ED
joanna: 05/17/2011
joanna: 5/17/2011
*FIELD* CD
Nara Sobreira: 3/29/2011
*FIELD* ED
carol: 05/16/2011
carol: 3/29/2011