Full text data of VIPAS39
VIPAS39
(C14orf133, SPE39, VIPAR)
[Confidence: low (only semi-automatic identification from reviews)]
Spermatogenesis-defective protein 39 homolog; hSPE-39 (VPS33B-interacting protein in apical-basolateral polarity regulator; VPS33B-interacting protein in polarity and apical restriction)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Spermatogenesis-defective protein 39 homolog; hSPE-39 (VPS33B-interacting protein in apical-basolateral polarity regulator; VPS33B-interacting protein in polarity and apical restriction)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9H9C1
ID SPE39_HUMAN Reviewed; 493 AA.
AC Q9H9C1; B4DPI6; O95434; Q9H7E1; Q9H9I9;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=Spermatogenesis-defective protein 39 homolog;
DE Short=hSPE-39;
DE AltName: Full=VPS33B-interacting protein in apical-basolateral polarity regulator;
DE AltName: Full=VPS33B-interacting protein in polarity and apical restriction;
GN Name=VIPAS39; Synonyms=C14orf133, SPE39, VIPAR;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-132, AND MASS
RP 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 [5]
RP FUNCTION, INTERACTION WITH VPS33A; VPS33B AND HOPS COMPLEX, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19109425; DOI=10.1091/mbc.E08-07-0728;
RA Zhu G.D., Salazar G., Zlatic S.A., Fiza B., Doucette M.M.,
RA Heilman C.J., Levey A.I., Faundez V., L'hernault S.W.;
RT "SPE-39 family proteins interact with the HOPS complex and function in
RT lysosomal delivery.";
RL Mol. Biol. Cell 20:1223-1240(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121, AND MASS
RP 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 [7]
RP FUNCTION, INTERACTION WITH RAB11A AND VPS33B, SUBCELLULAR LOCATION,
RP AND INVOLVEMENT IN ARCS1.
RX PubMed=20190753; DOI=10.1038/ng.538;
RA Cullinane A.R., Straatman-Iwanowska A., Zaucker A., Wakabayashi Y.,
RA Bruce C.K., Luo G., Rahman F., Gurakan F., Utine E., Ozkan T.B.,
RA Denecke J., Vukovic J., Di Rocco M., Mandel H., Cangul H.,
RA Matthews R.P., Thomas S.G., Rappoport J.Z., Arias I.M., Wolburg H.,
RA Knisely A.S., Kelly D.A., Muller F., Maher E.R., Gissen P.;
RT "Mutations in VIPAR cause an arthrogryposis, renal dysfunction and
RT cholestasis syndrome phenotype with defects in epithelial
RT polarization.";
RL Nat. Genet. 42:303-312(2010).
RN [8]
RP GENE NOMENCLATURE.
RX PubMed=21350494; DOI=10.1038/ng0311-176;
RA L'Hernault S.W., Faundez V.;
RT "On the endosomal function and gene nomenclature of human SPE-39.";
RL Nat. Genet. 43:176-176(2011).
CC -!- FUNCTION: May play a role in vesicular trafficking during
CC spermatogenesis (By similarity). Plays a role in lysosomal
CC trafficking, probably via association with the core HOPS complex
CC in a discrete population of endosomes. May play a role in
CC epithelial polarization through stabilization of apical membrane
CC protein content, possibly via the RAB11A-dependent apical
CC recycling pathway. Also involved in direct or indirect
CC transcriptional regulation of E-cadherin.
CC -!- SUBUNIT: Associates with the homotypic fusion and vacuole protein
CC sorting (HOPS) complex. Interacts with VPS33A and VPS33B.
CC Interacts with RAB11A.
CC -!- INTERACTION:
CC Q91W86:Vps11 (xeno); NbExp=3; IntAct=EBI-749080, EBI-2527812;
CC Q920Q4:Vps16 (xeno); NbExp=4; IntAct=EBI-749080, EBI-775797;
CC Q8R307:Vps18 (xeno); NbExp=5; IntAct=EBI-749080, EBI-2527788;
CC Q9H267:VPS33B; NbExp=20; IntAct=EBI-749080, EBI-749072;
CC P49754:VPS41; NbExp=4; IntAct=EBI-749080, EBI-2130459;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cytoplasmic
CC vesicle (By similarity). Early endosome. Recycling endosome. Late
CC endosome. Note=Colocalizes in clusters with VPS33B at cytoplasmic
CC organelles (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H9C1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H9C1-2; Sequence=VSP_043055;
CC Note=No experimental confirmation available;
CC -!- DISEASE: Arthrogryposis, renal dysfunction and cholestasis
CC syndrome 2 (ARCS2) [MIM:613404]: A multisystem disorder,
CC characterized by neurogenic arthrogryposis multiplex congenita,
CC renal tubular dysfunction and neonatal cholestasis with bile duct
CC hypoplasia and low gamma glutamyl transpeptidase activity.
CC Platelet dysfunction is common. Note=The disease is caused by
CC mutations affecting the gene represented in this entry. In liver,
CC CEACAM5 and ABCB11 are mislocalized and E-cadherin expression is
CC decreased.
CC -!- SIMILARITY: Belongs to the SPE39 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD09624.1; Type=Erroneous gene model prediction;
CC Sequence=BAB14951.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AK024661; BAB14951.1; ALT_INIT; mRNA.
DR EMBL; AK022769; BAB14237.1; -; mRNA.
DR EMBL; AK022925; BAB14310.1; -; mRNA.
DR EMBL; AK298354; BAG60598.1; -; mRNA.
DR EMBL; AF111168; AAD09624.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC015054; AAH15054.1; -; mRNA.
DR RefSeq; NP_001180243.1; NM_001193314.1.
DR RefSeq; NP_001180244.1; NM_001193315.1.
DR RefSeq; NP_001180245.1; NM_001193316.1.
DR RefSeq; NP_001180246.1; NM_001193317.1.
DR RefSeq; NP_071350.2; NM_022067.3.
DR UniGene; Hs.16157; -.
DR ProteinModelPortal; Q9H9C1; -.
DR IntAct; Q9H9C1; 10.
DR MINT; MINT-1451086; -.
DR PhosphoSite; Q9H9C1; -.
DR DMDM; 41016926; -.
DR PaxDb; Q9H9C1; -.
DR PRIDE; Q9H9C1; -.
DR DNASU; 63894; -.
DR Ensembl; ENST00000327028; ENSP00000313098; ENSG00000151445.
DR Ensembl; ENST00000343765; ENSP00000339122; ENSG00000151445.
DR Ensembl; ENST00000448935; ENSP00000404815; ENSG00000151445.
DR Ensembl; ENST00000553888; ENSP00000452181; ENSG00000151445.
DR Ensembl; ENST00000557658; ENSP00000452191; ENSG00000151445.
DR GeneID; 63894; -.
DR KEGG; hsa:63894; -.
DR UCSC; uc001xtt.2; human.
DR CTD; 63894; -.
DR GeneCards; GC14M077895; -.
DR HGNC; HGNC:20347; VIPAS39.
DR HPA; HPA003589; -.
DR HPA; HPA003593; -.
DR MIM; 613401; gene.
DR MIM; 613404; phenotype.
DR neXtProt; NX_Q9H9C1; -.
DR Orphanet; 2697; Arthrogryposis - renal dysfunction - cholestasis.
DR PharmGKB; PA165479332; -.
DR eggNOG; NOG147553; -.
DR HOGENOM; HOG000070044; -.
DR HOVERGEN; HBG051031; -.
DR InParanoid; Q9H9C1; -.
DR OrthoDB; EOG7RV9G5; -.
DR PhylomeDB; Q9H9C1; -.
DR GenomeRNAi; 63894; -.
DR NextBio; 65582; -.
DR PRO; PR:Q9H9C1; -.
DR ArrayExpress; Q9H9C1; -.
DR Bgee; Q9H9C1; -.
DR CleanEx; HS_C14orf133; -.
DR Genevestigator; Q9H9C1; -.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR019177; Golgin_subfamily_A_member_5.
DR Pfam; PF09787; Golgin_A5; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm;
KW Cytoplasmic vesicle; Differentiation; Endosome; Phosphoprotein;
KW Protein transport; Reference proteome; Spermatogenesis; Transcription;
KW Transcription regulation; Transport.
FT CHAIN 1 493 Spermatogenesis-defective protein 39
FT homolog.
FT /FTId=PRO_0000089935.
FT MOD_RES 21 21 Phosphothreonine (By similarity).
FT MOD_RES 121 121 Phosphoserine.
FT MOD_RES 124 124 Phosphoserine (By similarity).
FT MOD_RES 132 132 Phosphothreonine.
FT VAR_SEQ 67 115 Missing (in isoform 2).
FT /FTId=VSP_043055.
FT CONFLICT 280 280 L -> S (in Ref. 1; BAB14237).
SQ SEQUENCE 493 AA; 57005 MW; CF05C38EB922D192 CRC64;
MNRTKGDEEE YWNSSKFKAF TFDDEDDELS QLKESKRAVN SLRDFVDDDD DDDLERVSWS
GEPVGSISWS IRETAGNSGS THEGREQLKS RNSFSSYAQL PKPTSTYSLS SFFRGRTRPG
SFQSLSDALS DTPAKSYAPE LGRPKGEYRD YSNDWSPSDT VRRLRKGKVC SLERFRSLQD
KLQLLEEAVS MHDGNVITAV LIFLKRTLSK EILFRELEVR QVALRHLIHF LKEIGDQKLL
LDLFRFLDRT EELALSHYRE HLNIQDPDKR KEFLKTCVGL PFSAEDSAHI QDHYTLLERQ
IIIEANDRHL ESAGQTEIFR KHPRKASILN MPLVTTLFYS CFYHYTEAEG TFSSPVNLKK
TFKIPDKQYV LTALAARAKL RAWNDVDALF TTKNWLGYTK KRAPIGFHRV VEILHKNNAP
VQILQEYVNL VEDVDTKLNL ATKFKCHDVV IDTYRDLKDR QQLLAYRSKV DKGSAEEEKI
DALLSSSQIR WKN
//
ID SPE39_HUMAN Reviewed; 493 AA.
AC Q9H9C1; B4DPI6; O95434; Q9H7E1; Q9H9I9;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=Spermatogenesis-defective protein 39 homolog;
DE Short=hSPE-39;
DE AltName: Full=VPS33B-interacting protein in apical-basolateral polarity regulator;
DE AltName: Full=VPS33B-interacting protein in polarity and apical restriction;
GN Name=VIPAS39; Synonyms=C14orf133, SPE39, VIPAR;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-132, AND MASS
RP 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 [5]
RP FUNCTION, INTERACTION WITH VPS33A; VPS33B AND HOPS COMPLEX, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19109425; DOI=10.1091/mbc.E08-07-0728;
RA Zhu G.D., Salazar G., Zlatic S.A., Fiza B., Doucette M.M.,
RA Heilman C.J., Levey A.I., Faundez V., L'hernault S.W.;
RT "SPE-39 family proteins interact with the HOPS complex and function in
RT lysosomal delivery.";
RL Mol. Biol. Cell 20:1223-1240(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121, AND MASS
RP 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 [7]
RP FUNCTION, INTERACTION WITH RAB11A AND VPS33B, SUBCELLULAR LOCATION,
RP AND INVOLVEMENT IN ARCS1.
RX PubMed=20190753; DOI=10.1038/ng.538;
RA Cullinane A.R., Straatman-Iwanowska A., Zaucker A., Wakabayashi Y.,
RA Bruce C.K., Luo G., Rahman F., Gurakan F., Utine E., Ozkan T.B.,
RA Denecke J., Vukovic J., Di Rocco M., Mandel H., Cangul H.,
RA Matthews R.P., Thomas S.G., Rappoport J.Z., Arias I.M., Wolburg H.,
RA Knisely A.S., Kelly D.A., Muller F., Maher E.R., Gissen P.;
RT "Mutations in VIPAR cause an arthrogryposis, renal dysfunction and
RT cholestasis syndrome phenotype with defects in epithelial
RT polarization.";
RL Nat. Genet. 42:303-312(2010).
RN [8]
RP GENE NOMENCLATURE.
RX PubMed=21350494; DOI=10.1038/ng0311-176;
RA L'Hernault S.W., Faundez V.;
RT "On the endosomal function and gene nomenclature of human SPE-39.";
RL Nat. Genet. 43:176-176(2011).
CC -!- FUNCTION: May play a role in vesicular trafficking during
CC spermatogenesis (By similarity). Plays a role in lysosomal
CC trafficking, probably via association with the core HOPS complex
CC in a discrete population of endosomes. May play a role in
CC epithelial polarization through stabilization of apical membrane
CC protein content, possibly via the RAB11A-dependent apical
CC recycling pathway. Also involved in direct or indirect
CC transcriptional regulation of E-cadherin.
CC -!- SUBUNIT: Associates with the homotypic fusion and vacuole protein
CC sorting (HOPS) complex. Interacts with VPS33A and VPS33B.
CC Interacts with RAB11A.
CC -!- INTERACTION:
CC Q91W86:Vps11 (xeno); NbExp=3; IntAct=EBI-749080, EBI-2527812;
CC Q920Q4:Vps16 (xeno); NbExp=4; IntAct=EBI-749080, EBI-775797;
CC Q8R307:Vps18 (xeno); NbExp=5; IntAct=EBI-749080, EBI-2527788;
CC Q9H267:VPS33B; NbExp=20; IntAct=EBI-749080, EBI-749072;
CC P49754:VPS41; NbExp=4; IntAct=EBI-749080, EBI-2130459;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cytoplasmic
CC vesicle (By similarity). Early endosome. Recycling endosome. Late
CC endosome. Note=Colocalizes in clusters with VPS33B at cytoplasmic
CC organelles (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H9C1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H9C1-2; Sequence=VSP_043055;
CC Note=No experimental confirmation available;
CC -!- DISEASE: Arthrogryposis, renal dysfunction and cholestasis
CC syndrome 2 (ARCS2) [MIM:613404]: A multisystem disorder,
CC characterized by neurogenic arthrogryposis multiplex congenita,
CC renal tubular dysfunction and neonatal cholestasis with bile duct
CC hypoplasia and low gamma glutamyl transpeptidase activity.
CC Platelet dysfunction is common. Note=The disease is caused by
CC mutations affecting the gene represented in this entry. In liver,
CC CEACAM5 and ABCB11 are mislocalized and E-cadherin expression is
CC decreased.
CC -!- SIMILARITY: Belongs to the SPE39 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD09624.1; Type=Erroneous gene model prediction;
CC Sequence=BAB14951.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
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DR EMBL; AK024661; BAB14951.1; ALT_INIT; mRNA.
DR EMBL; AK022769; BAB14237.1; -; mRNA.
DR EMBL; AK022925; BAB14310.1; -; mRNA.
DR EMBL; AK298354; BAG60598.1; -; mRNA.
DR EMBL; AF111168; AAD09624.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC015054; AAH15054.1; -; mRNA.
DR RefSeq; NP_001180243.1; NM_001193314.1.
DR RefSeq; NP_001180244.1; NM_001193315.1.
DR RefSeq; NP_001180245.1; NM_001193316.1.
DR RefSeq; NP_001180246.1; NM_001193317.1.
DR RefSeq; NP_071350.2; NM_022067.3.
DR UniGene; Hs.16157; -.
DR ProteinModelPortal; Q9H9C1; -.
DR IntAct; Q9H9C1; 10.
DR MINT; MINT-1451086; -.
DR PhosphoSite; Q9H9C1; -.
DR DMDM; 41016926; -.
DR PaxDb; Q9H9C1; -.
DR PRIDE; Q9H9C1; -.
DR DNASU; 63894; -.
DR Ensembl; ENST00000327028; ENSP00000313098; ENSG00000151445.
DR Ensembl; ENST00000343765; ENSP00000339122; ENSG00000151445.
DR Ensembl; ENST00000448935; ENSP00000404815; ENSG00000151445.
DR Ensembl; ENST00000553888; ENSP00000452181; ENSG00000151445.
DR Ensembl; ENST00000557658; ENSP00000452191; ENSG00000151445.
DR GeneID; 63894; -.
DR KEGG; hsa:63894; -.
DR UCSC; uc001xtt.2; human.
DR CTD; 63894; -.
DR GeneCards; GC14M077895; -.
DR HGNC; HGNC:20347; VIPAS39.
DR HPA; HPA003589; -.
DR HPA; HPA003593; -.
DR MIM; 613401; gene.
DR MIM; 613404; phenotype.
DR neXtProt; NX_Q9H9C1; -.
DR Orphanet; 2697; Arthrogryposis - renal dysfunction - cholestasis.
DR PharmGKB; PA165479332; -.
DR eggNOG; NOG147553; -.
DR HOGENOM; HOG000070044; -.
DR HOVERGEN; HBG051031; -.
DR InParanoid; Q9H9C1; -.
DR OrthoDB; EOG7RV9G5; -.
DR PhylomeDB; Q9H9C1; -.
DR GenomeRNAi; 63894; -.
DR NextBio; 65582; -.
DR PRO; PR:Q9H9C1; -.
DR ArrayExpress; Q9H9C1; -.
DR Bgee; Q9H9C1; -.
DR CleanEx; HS_C14orf133; -.
DR Genevestigator; Q9H9C1; -.
DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR019177; Golgin_subfamily_A_member_5.
DR Pfam; PF09787; Golgin_A5; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm;
KW Cytoplasmic vesicle; Differentiation; Endosome; Phosphoprotein;
KW Protein transport; Reference proteome; Spermatogenesis; Transcription;
KW Transcription regulation; Transport.
FT CHAIN 1 493 Spermatogenesis-defective protein 39
FT homolog.
FT /FTId=PRO_0000089935.
FT MOD_RES 21 21 Phosphothreonine (By similarity).
FT MOD_RES 121 121 Phosphoserine.
FT MOD_RES 124 124 Phosphoserine (By similarity).
FT MOD_RES 132 132 Phosphothreonine.
FT VAR_SEQ 67 115 Missing (in isoform 2).
FT /FTId=VSP_043055.
FT CONFLICT 280 280 L -> S (in Ref. 1; BAB14237).
SQ SEQUENCE 493 AA; 57005 MW; CF05C38EB922D192 CRC64;
MNRTKGDEEE YWNSSKFKAF TFDDEDDELS QLKESKRAVN SLRDFVDDDD DDDLERVSWS
GEPVGSISWS IRETAGNSGS THEGREQLKS RNSFSSYAQL PKPTSTYSLS SFFRGRTRPG
SFQSLSDALS DTPAKSYAPE LGRPKGEYRD YSNDWSPSDT VRRLRKGKVC SLERFRSLQD
KLQLLEEAVS MHDGNVITAV LIFLKRTLSK EILFRELEVR QVALRHLIHF LKEIGDQKLL
LDLFRFLDRT EELALSHYRE HLNIQDPDKR KEFLKTCVGL PFSAEDSAHI QDHYTLLERQ
IIIEANDRHL ESAGQTEIFR KHPRKASILN MPLVTTLFYS CFYHYTEAEG TFSSPVNLKK
TFKIPDKQYV LTALAARAKL RAWNDVDALF TTKNWLGYTK KRAPIGFHRV VEILHKNNAP
VQILQEYVNL VEDVDTKLNL ATKFKCHDVV IDTYRDLKDR QQLLAYRSKV DKGSAEEEKI
DALLSSSQIR WKN
//
MIM
613401
*RECORD*
*FIELD* NO
613401
*FIELD* TI
*613401 VPS33B-INTERACTING PROTEIN, APICAL-BASOLATERAL POLARITY REGULATOR,
SPE39 HOMOLOG; VIPAS39
read more;;VPS33B-INTERACTING PROTEIN, APICAL-BASOLATERAL POLARITY REGULATOR;
VIPAR;;
SPE39, C. ELEGANS, HOMOLOG OF; SPE39;;
CHROMOSOME 14 OPEN READING FRAME 133; C14ORF133
*FIELD* TX
DESCRIPTION
VIPAR is involved in intracellular sorting and trafficking of lysosomal
proteins (Zhu et al., 2009).
CLONING
By searching for orthologs of C. elegans Spe39, followed by PCR of a
brain cDNA library, Zhu et al. (2009) cloned VIPAR, which they called
SPE39. Immunofluorescence analysis of HEK293 cells localized SPE39 to 1
to 3 perinuclear puncta per cell, which proved to be a small subset of
VPS33A (610034)-and VPS33B (608552)-positive vesicles. Database analysis
revealed SPE39 orthologs only in animals.
MAPPING
By genomic sequence analysis, Heilig et al. (2003) mapped the VIPAR gene
to chromosome 14q24.3.
GENE FUNCTION
Homotypic fusion and vacuole protein sorting (HOPS) complexes regulate
intracellular vesicle docking through interaction with SNAREs (see
604026). By immunoprecipitation analysis and Western blot analysis of
sucrose gradient fractions of HeLa and HEK293 cells, Zhu et al. (2009)
showed that SPE39 interacted with a number of endogenous or
cotransfected HOPS components, including VPS33A and VPS33B. Knockdown of
SPE39 in HEK293 cells via RNA interference affected the morphology and
sorting of RAB11 (see 605570)- and syntaxin-13 (STX13, or STX12,
606892)-positive recycling endosomes and RAB7 (602298)-, syntaxin-7
(STX7; 603217), and syntaxin-8 (STX8; 604203)-positive late endosomes.
It did not alter Golgi-to-sorting endosome traffic. SPE39 knockdown in
HeLa cells perturbed M6PR (154540) trafficking and M6PR-mediated
delivery of the lysosomal enzyme cathepsin D (CTSD; 116840), and it
delayed degradation of internalized EGFR (131550). Zhu et al. (2009)
concluded that VIPAR regulates the sorting and trafficking of lysosome
resident proteins along the sorting and recycling pathways.
In a yeast 2-hybrid screen to identify VPS33B (608552)-interacting
proteins, Cullinane et al. (2010) found that the protein encoded by
C14ORF133, which they designated VIPAR, had highest priority based on
bioinformatic analyses of homology and putative function.
Coimmunoprecipitation studies in transfected HEK293 cells confirmed the
interaction between overexpressed VPS33B and VIPAR, with formation of
functional VPS33B-VIPAR complexes at cytoplasmic organelles that
interacted with RAB11A (605570). Knockdown of vipar in zebrafish
resulted in biliary excretion and E-cadherin (CDH1; 192090) defects
similar to those in individuals with ARC syndrome (see ARCS1, 208085)
caused by mutation in VPS33B or VIPAR (see MOLECULAR GENETICS section).
Vipar- and Vps33b-deficient mouse inner medullary collecting duct
(mIMCD-3) cells expressed membrane proteins abnormally and had
structural and functional tight junction defects. Abnormal Ceacam5
(114890) expression was due to missorting toward lysosomal degradation,
but reduced E-cadherin levels were associated with transcriptional
downregulation. Cullinane et al. (2010) concluded that the VPS33B-VIPAR
complex has diverse functions in the pathways regulating
apical-basolateral polarity in the liver and kidney.
MOLECULAR GENETICS
In 3 probands with arthrogryposis, renal dysfunction, and cholestasis-2
(ARCS2; 613404) mapping to the VIPAR locus on chromosome 14q24.3 and in
4 additional probands who did not have mutations in the known ARCS1
(208085) gene, VPS33B (608552), Cullinane et al. (2010) identified
homozygosity or compound heterozygosity for mutations in the VIPAR gene
(see, e.g., 613401.0001-613401.0005). All of the mutations were
predicted to eliminate normal protein production because of early
message termination and nonsense-mediated mRNA decay or because of
translation failure; in addition, all of the mutations segregated with
disease in the families and were not found in at least 200 ethnically
matched control chromosomes.
*FIELD* AV
.0001
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2
VIPAS39, GLN179TER
In a Turkish proband with arthrogryposis, renal dysfunction, and
cholestasis-2 (613404), Cullinane et al. (2010) identified homozygosity
for a 535C-T transition in the VIPAR gene, resulting in a gln179-to-ter
(Q179X) substitution. The mutation segregated with disease in the family
and was not found in at least 200 ethnically matched chromosomes.
.0002
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2
VIPAS39, 5-BP DEL, NT748
In a Croatian proband with arthrogryposis, renal dysfunction, and
cholestasis-2 (613404), Cullinane et al. (2010) identified homozygosity
for a 5-bp deletion (748delACAGA) in the VIPAR gene, causing a
frameshift and a premature termination codon. The mutation segregated
with disease in the family and was not found in at least 200 ethnically
matched chromosomes.
.0003
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2
VIPAS39, ARG220TER
In an Italian proband with arthrogryposis, renal dysfunction, and
cholestasis-2 (613404), Cullinane et al. (2010) identified homozygosity
for a 658C-T transition in the VIPAR gene, resulting in an arg220-to-ter
(R220X) substitution. A Turkish ARCS proband was found to be compound
heterozygous for R220X and an 873C-T transition in the VIPAR gene,
resulting in a gln291-to-ter (Q291X; 613404.0004) substitution. Both
mutations segregated with disease in the families and were not found in
at least 200 ethnically matched chromosomes, respectively.
.0004
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2
VIPAS39, GLN291TER
See 613401.0003 and Cullinane et al. (2010).
.0005
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2
VIPAS39, MET1ARG
In a Turkish proband with arthrogryposis, renal dysfunction, and
cholestasis-2 (613404), Cullinane et al. (2010) identified homozygosity
for a 2T-G transversion in the VIPAR gene, resulting in a met1-to-arg
(M1R) substitution at the start codon, predicted to cause failure of
translation. The mutation segregated with disease in the family and was
not found in at least 200 ethnically matched chromosomes.
*FIELD* RF
1. Cullinane, A. R.; Straatman-Iwanowska, A.; Zaucker, A.; Wakabayashi,
Y.; Bruce, C. K.; Luo, G.; Rahman, F.; Gurakan, F.; Utine, E.; Ozkan,
T. B.; Denecke, J.; Vukovic, J.; and 13 others: Mutations in VIPAR
cause an arthrogryposis, renal dysfunction and cholestasis syndrome
phenotype with defects in epithelial polarization. Nature Genet. 42:
303-312, 2010. Note: Erratum: Nature Genet. 43: 277 only, 2011.
2. Heilig, R.; Eckenberg, R.; Petit, J.-L.; Fonknechten, N.; Da Silva,
C.; Cattolico, L.; Levy, M.; Barbe, V.; de Berardinis, V.; Ureta-Vidal,
A.; Pelletier, E.; Vico, V; and 87 others: The DNA sequence and
analysis of human chromosome 14. Nature 421: 601-607, 2003.
3. Zhu, G.; Salazar, G.; Zlatic, S. A.; Fiza, B.; Doucette, M. M.;
Heilman, C. J.; Levey, A. I.; Faundez, V.; L'Hernault, S. W.: SPE-39
family proteins interact with the HOPS complex and function in lysosomal
delivery. Molec. Biol. Cell 20: 1223-1240, 2009.
*FIELD* CN
Marla J. F. O'Neill - updated: 5/13/2010
*FIELD* CD
Patricia A. Hartz: 5/12/2010
*FIELD* ED
carol: 11/19/2013
joanna: 8/5/2013
carol: 3/21/2011
terry: 12/6/2010
terry: 5/14/2010
carol: 5/13/2010
mgross: 5/12/2010
*RECORD*
*FIELD* NO
613401
*FIELD* TI
*613401 VPS33B-INTERACTING PROTEIN, APICAL-BASOLATERAL POLARITY REGULATOR,
SPE39 HOMOLOG; VIPAS39
read more;;VPS33B-INTERACTING PROTEIN, APICAL-BASOLATERAL POLARITY REGULATOR;
VIPAR;;
SPE39, C. ELEGANS, HOMOLOG OF; SPE39;;
CHROMOSOME 14 OPEN READING FRAME 133; C14ORF133
*FIELD* TX
DESCRIPTION
VIPAR is involved in intracellular sorting and trafficking of lysosomal
proteins (Zhu et al., 2009).
CLONING
By searching for orthologs of C. elegans Spe39, followed by PCR of a
brain cDNA library, Zhu et al. (2009) cloned VIPAR, which they called
SPE39. Immunofluorescence analysis of HEK293 cells localized SPE39 to 1
to 3 perinuclear puncta per cell, which proved to be a small subset of
VPS33A (610034)-and VPS33B (608552)-positive vesicles. Database analysis
revealed SPE39 orthologs only in animals.
MAPPING
By genomic sequence analysis, Heilig et al. (2003) mapped the VIPAR gene
to chromosome 14q24.3.
GENE FUNCTION
Homotypic fusion and vacuole protein sorting (HOPS) complexes regulate
intracellular vesicle docking through interaction with SNAREs (see
604026). By immunoprecipitation analysis and Western blot analysis of
sucrose gradient fractions of HeLa and HEK293 cells, Zhu et al. (2009)
showed that SPE39 interacted with a number of endogenous or
cotransfected HOPS components, including VPS33A and VPS33B. Knockdown of
SPE39 in HEK293 cells via RNA interference affected the morphology and
sorting of RAB11 (see 605570)- and syntaxin-13 (STX13, or STX12,
606892)-positive recycling endosomes and RAB7 (602298)-, syntaxin-7
(STX7; 603217), and syntaxin-8 (STX8; 604203)-positive late endosomes.
It did not alter Golgi-to-sorting endosome traffic. SPE39 knockdown in
HeLa cells perturbed M6PR (154540) trafficking and M6PR-mediated
delivery of the lysosomal enzyme cathepsin D (CTSD; 116840), and it
delayed degradation of internalized EGFR (131550). Zhu et al. (2009)
concluded that VIPAR regulates the sorting and trafficking of lysosome
resident proteins along the sorting and recycling pathways.
In a yeast 2-hybrid screen to identify VPS33B (608552)-interacting
proteins, Cullinane et al. (2010) found that the protein encoded by
C14ORF133, which they designated VIPAR, had highest priority based on
bioinformatic analyses of homology and putative function.
Coimmunoprecipitation studies in transfected HEK293 cells confirmed the
interaction between overexpressed VPS33B and VIPAR, with formation of
functional VPS33B-VIPAR complexes at cytoplasmic organelles that
interacted with RAB11A (605570). Knockdown of vipar in zebrafish
resulted in biliary excretion and E-cadherin (CDH1; 192090) defects
similar to those in individuals with ARC syndrome (see ARCS1, 208085)
caused by mutation in VPS33B or VIPAR (see MOLECULAR GENETICS section).
Vipar- and Vps33b-deficient mouse inner medullary collecting duct
(mIMCD-3) cells expressed membrane proteins abnormally and had
structural and functional tight junction defects. Abnormal Ceacam5
(114890) expression was due to missorting toward lysosomal degradation,
but reduced E-cadherin levels were associated with transcriptional
downregulation. Cullinane et al. (2010) concluded that the VPS33B-VIPAR
complex has diverse functions in the pathways regulating
apical-basolateral polarity in the liver and kidney.
MOLECULAR GENETICS
In 3 probands with arthrogryposis, renal dysfunction, and cholestasis-2
(ARCS2; 613404) mapping to the VIPAR locus on chromosome 14q24.3 and in
4 additional probands who did not have mutations in the known ARCS1
(208085) gene, VPS33B (608552), Cullinane et al. (2010) identified
homozygosity or compound heterozygosity for mutations in the VIPAR gene
(see, e.g., 613401.0001-613401.0005). All of the mutations were
predicted to eliminate normal protein production because of early
message termination and nonsense-mediated mRNA decay or because of
translation failure; in addition, all of the mutations segregated with
disease in the families and were not found in at least 200 ethnically
matched control chromosomes.
*FIELD* AV
.0001
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2
VIPAS39, GLN179TER
In a Turkish proband with arthrogryposis, renal dysfunction, and
cholestasis-2 (613404), Cullinane et al. (2010) identified homozygosity
for a 535C-T transition in the VIPAR gene, resulting in a gln179-to-ter
(Q179X) substitution. The mutation segregated with disease in the family
and was not found in at least 200 ethnically matched chromosomes.
.0002
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2
VIPAS39, 5-BP DEL, NT748
In a Croatian proband with arthrogryposis, renal dysfunction, and
cholestasis-2 (613404), Cullinane et al. (2010) identified homozygosity
for a 5-bp deletion (748delACAGA) in the VIPAR gene, causing a
frameshift and a premature termination codon. The mutation segregated
with disease in the family and was not found in at least 200 ethnically
matched chromosomes.
.0003
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2
VIPAS39, ARG220TER
In an Italian proband with arthrogryposis, renal dysfunction, and
cholestasis-2 (613404), Cullinane et al. (2010) identified homozygosity
for a 658C-T transition in the VIPAR gene, resulting in an arg220-to-ter
(R220X) substitution. A Turkish ARCS proband was found to be compound
heterozygous for R220X and an 873C-T transition in the VIPAR gene,
resulting in a gln291-to-ter (Q291X; 613404.0004) substitution. Both
mutations segregated with disease in the families and were not found in
at least 200 ethnically matched chromosomes, respectively.
.0004
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2
VIPAS39, GLN291TER
See 613401.0003 and Cullinane et al. (2010).
.0005
ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2
VIPAS39, MET1ARG
In a Turkish proband with arthrogryposis, renal dysfunction, and
cholestasis-2 (613404), Cullinane et al. (2010) identified homozygosity
for a 2T-G transversion in the VIPAR gene, resulting in a met1-to-arg
(M1R) substitution at the start codon, predicted to cause failure of
translation. The mutation segregated with disease in the family and was
not found in at least 200 ethnically matched chromosomes.
*FIELD* RF
1. Cullinane, A. R.; Straatman-Iwanowska, A.; Zaucker, A.; Wakabayashi,
Y.; Bruce, C. K.; Luo, G.; Rahman, F.; Gurakan, F.; Utine, E.; Ozkan,
T. B.; Denecke, J.; Vukovic, J.; and 13 others: Mutations in VIPAR
cause an arthrogryposis, renal dysfunction and cholestasis syndrome
phenotype with defects in epithelial polarization. Nature Genet. 42:
303-312, 2010. Note: Erratum: Nature Genet. 43: 277 only, 2011.
2. Heilig, R.; Eckenberg, R.; Petit, J.-L.; Fonknechten, N.; Da Silva,
C.; Cattolico, L.; Levy, M.; Barbe, V.; de Berardinis, V.; Ureta-Vidal,
A.; Pelletier, E.; Vico, V; and 87 others: The DNA sequence and
analysis of human chromosome 14. Nature 421: 601-607, 2003.
3. Zhu, G.; Salazar, G.; Zlatic, S. A.; Fiza, B.; Doucette, M. M.;
Heilman, C. J.; Levey, A. I.; Faundez, V.; L'Hernault, S. W.: SPE-39
family proteins interact with the HOPS complex and function in lysosomal
delivery. Molec. Biol. Cell 20: 1223-1240, 2009.
*FIELD* CN
Marla J. F. O'Neill - updated: 5/13/2010
*FIELD* CD
Patricia A. Hartz: 5/12/2010
*FIELD* ED
carol: 11/19/2013
joanna: 8/5/2013
carol: 3/21/2011
terry: 12/6/2010
terry: 5/14/2010
carol: 5/13/2010
mgross: 5/12/2010
MIM
613404
*RECORD*
*FIELD* NO
613404
*FIELD* TI
#613404 ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2; ARCS2
*FIELD* TX
A number sign (#) is used with this entry because arthrogryposis, renal
read moredysfunction, and cholestasis-2 (ARCS2) is caused by homozygous or
compound heterozygous mutation in the VIPAR gene (613401) on chromosome
14q24.3.
For a general phenotypic description and a discussion of genetic
heterogeneity of ARCS, see ARCS1 (208085).
MAPPING
In 3 probands with arthrogryposis, renal dysfunction, and cholestasis-2
(ARCS2) who did not have mutations in the known ARCS1 gene, VPS33B
(608552), Cullinane et al. (2010) performed a genomewide linkage screen
and identified homozygosity at the VIPAR locus on chromosome
14q24.3-q31.
MOLECULAR GENETICS
In 3 probands with arthrogryposis, renal dysfunction, and cholestasis
(ARCS2) mapping to the VIPAR locus on chromosome 14q24.3 and in 4
additional probands who did not have mutations in the known ARCS1 gene,
VPS33B (608552), Cullinane et al. (2010) identified homozygosity or
compound heterozygosity for mutations in the VIPAR gene (see, e.g.,
613401.0001-613401.0005). The authors detected no differences in
clinical symptoms, signs, or disease course between ARCS patients with
mutations in VIPAR compared to patients with mutations in VPS33B.
*FIELD* RF
1. Cullinane, A. R.; Straatman-Iwanowska, A.; Zaucker, A.; Wakabayashi,
Y.; Bruce, C. K.; Luo, G.; Rahman, F.; Gurakan, F.; Utine, E.; Ozkan,
T. B.; Denecke, J.; Vukovic, J.; and 13 others: Mutations in VIPAR
cause an arthrogryposis, renal dysfunction and cholestasis syndrome
phenotype with defects in epithelial polarization. Nature Genet. 42:
303-312, 2010. Note: Erratum: Nature Genet. 43: 277 only, 2011.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Other];
Failure to thrive
HEAD AND NECK:
[Head];
Microcephaly;
[Face];
Sloping forehead;
[Ears];
Low-set ears
CARDIOVASCULAR:
[Heart];
Structural cardiac defects (uncommon);
Atrial septal defects;
Ventricular septal defects;
Persistent foramen ovale;
Right ventricular hypertrophy (report in 2 sibs)
ABDOMEN:
[Liver];
Cholestatic liver disease;
Bile duct abnormalities (paucity, proliferation);
Giant cell hepatitis;
Pigmentary deposits;
Portal tract fibrosis
GENITOURINARY:
[Kidneys];
Renal tubular acidosis;
Fanconi syndrome;
Nephropathy;
Nephrocalcinosis;
Nephrogenic diabetes insipidus (less common);
Renal tubular degeneration
SKELETAL:
Arthrogryposis multiplex congenita;
Fractures at birth;
[Pelvis];
Hip dysplasia;
[Feet];
Talipes calcaneovalgus
SKIN, NAILS, HAIR:
[Skin];
Ichthyosis;
Jaundice
NEUROLOGIC:
[Central nervous system];
Global developmental delay;
Hypotonia;
Lissencephaly (reported in 1 patient)
METABOLIC FEATURES:
Metabolic acidosis
HEMATOLOGY:
Severe bleeding after biopsies (uncommon)
IMMUNOLOGY:
Recurrent febrile illnesses;
B and T cell defects (reported in 2 sibs)
LABORATORY ABNORMALITIES:
Conjugated hyperbilirubinemia;
Abnormal liver function tests
MISCELLANEOUS:
Death in infancy, usually from sepsis, dehydration, or acidosis
MOLECULAR BASIS:
Caused by mutation in the VPS33B-interacting protein, apical-basolateral
polarity regulator gene (VIPAR, 613401.0001)
*FIELD* CD
Marla J. F. O'Neill: 12/30/2011
*FIELD* ED
joanna: 12/30/2011
*FIELD* CD
Marla J. F. O'Neill: 5/13/2010
*FIELD* ED
carol: 10/10/2012
terry: 5/14/2010
carol: 5/13/2010
*RECORD*
*FIELD* NO
613404
*FIELD* TI
#613404 ARTHROGRYPOSIS, RENAL DYSFUNCTION, AND CHOLESTASIS 2; ARCS2
*FIELD* TX
A number sign (#) is used with this entry because arthrogryposis, renal
read moredysfunction, and cholestasis-2 (ARCS2) is caused by homozygous or
compound heterozygous mutation in the VIPAR gene (613401) on chromosome
14q24.3.
For a general phenotypic description and a discussion of genetic
heterogeneity of ARCS, see ARCS1 (208085).
MAPPING
In 3 probands with arthrogryposis, renal dysfunction, and cholestasis-2
(ARCS2) who did not have mutations in the known ARCS1 gene, VPS33B
(608552), Cullinane et al. (2010) performed a genomewide linkage screen
and identified homozygosity at the VIPAR locus on chromosome
14q24.3-q31.
MOLECULAR GENETICS
In 3 probands with arthrogryposis, renal dysfunction, and cholestasis
(ARCS2) mapping to the VIPAR locus on chromosome 14q24.3 and in 4
additional probands who did not have mutations in the known ARCS1 gene,
VPS33B (608552), Cullinane et al. (2010) identified homozygosity or
compound heterozygosity for mutations in the VIPAR gene (see, e.g.,
613401.0001-613401.0005). The authors detected no differences in
clinical symptoms, signs, or disease course between ARCS patients with
mutations in VIPAR compared to patients with mutations in VPS33B.
*FIELD* RF
1. Cullinane, A. R.; Straatman-Iwanowska, A.; Zaucker, A.; Wakabayashi,
Y.; Bruce, C. K.; Luo, G.; Rahman, F.; Gurakan, F.; Utine, E.; Ozkan,
T. B.; Denecke, J.; Vukovic, J.; and 13 others: Mutations in VIPAR
cause an arthrogryposis, renal dysfunction and cholestasis syndrome
phenotype with defects in epithelial polarization. Nature Genet. 42:
303-312, 2010. Note: Erratum: Nature Genet. 43: 277 only, 2011.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Other];
Failure to thrive
HEAD AND NECK:
[Head];
Microcephaly;
[Face];
Sloping forehead;
[Ears];
Low-set ears
CARDIOVASCULAR:
[Heart];
Structural cardiac defects (uncommon);
Atrial septal defects;
Ventricular septal defects;
Persistent foramen ovale;
Right ventricular hypertrophy (report in 2 sibs)
ABDOMEN:
[Liver];
Cholestatic liver disease;
Bile duct abnormalities (paucity, proliferation);
Giant cell hepatitis;
Pigmentary deposits;
Portal tract fibrosis
GENITOURINARY:
[Kidneys];
Renal tubular acidosis;
Fanconi syndrome;
Nephropathy;
Nephrocalcinosis;
Nephrogenic diabetes insipidus (less common);
Renal tubular degeneration
SKELETAL:
Arthrogryposis multiplex congenita;
Fractures at birth;
[Pelvis];
Hip dysplasia;
[Feet];
Talipes calcaneovalgus
SKIN, NAILS, HAIR:
[Skin];
Ichthyosis;
Jaundice
NEUROLOGIC:
[Central nervous system];
Global developmental delay;
Hypotonia;
Lissencephaly (reported in 1 patient)
METABOLIC FEATURES:
Metabolic acidosis
HEMATOLOGY:
Severe bleeding after biopsies (uncommon)
IMMUNOLOGY:
Recurrent febrile illnesses;
B and T cell defects (reported in 2 sibs)
LABORATORY ABNORMALITIES:
Conjugated hyperbilirubinemia;
Abnormal liver function tests
MISCELLANEOUS:
Death in infancy, usually from sepsis, dehydration, or acidosis
MOLECULAR BASIS:
Caused by mutation in the VPS33B-interacting protein, apical-basolateral
polarity regulator gene (VIPAR, 613401.0001)
*FIELD* CD
Marla J. F. O'Neill: 12/30/2011
*FIELD* ED
joanna: 12/30/2011
*FIELD* CD
Marla J. F. O'Neill: 5/13/2010
*FIELD* ED
carol: 10/10/2012
terry: 5/14/2010
carol: 5/13/2010