Full text data of VPS37A
VPS37A
(HCRP1)
[Confidence: low (only semi-automatic identification from reviews)]
Vacuolar protein sorting-associated protein 37A; hVps37A (ESCRT-I complex subunit VPS37A; Hepatocellular carcinoma-related protein 1)
Vacuolar protein sorting-associated protein 37A; hVps37A (ESCRT-I complex subunit VPS37A; Hepatocellular carcinoma-related protein 1)
UniProt
Q8NEZ2
ID VP37A_HUMAN Reviewed; 397 AA.
AC Q8NEZ2; Q336D5; Q6NW27; Q8N3D7; Q8TBL7; Q96DL9;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2002, sequence version 1.
DT 22-JAN-2014, entry version 92.
DE RecName: Full=Vacuolar protein sorting-associated protein 37A;
DE Short=hVps37A;
DE AltName: Full=ESCRT-I complex subunit VPS37A;
DE AltName: Full=Hepatocellular carcinoma-related protein 1;
GN Name=VPS37A; Synonyms=HCRP1;
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] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=14623289; DOI=10.1016/j.bbrc.2003.10.109;
RA Xu Z., Liang L., Wang H., Li T., Zhao M.;
RT "HCRP1, a novel gene that is downregulated in hepatocellular
RT carcinoma, encodes a growth-inhibitory protein.";
RL Biochem. Biophys. Res. Commun. 311:1057-1066(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovium;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Prostate;
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 [5]
RP INTERACTION WITH TSG101.
RX PubMed=15218037; DOI=10.1074/jbc.M405226200;
RA Stuchell M.D., Garrus J.E., Mueller B., Stray K.M., Ghaffarian S.,
RA McKinnon R., Kraeusslich H.-G., Morham S.G., Sundquist W.I.;
RT "The human endosomal sorting complex required for transport (ESCRT-I)
RT and its role in HIV-1 budding.";
RL J. Biol. Chem. 279:36059-36071(2004).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TSG101; VPS28 AND
RP HGS.
RX PubMed=15240819; DOI=10.1091/mbc.E04-03-0250;
RA Bache K.G., Slagsvold T., Cabezas A., Rosendal K.R., Raiborg C.,
RA Stenmark H.;
RT "The growth-regulatory protein HCRP1/hVps37A is a subunit of mammalian
RT ESCRT-I and mediates receptor down-regulation.";
RL Mol. Biol. Cell 15:4337-4346(2004).
RN [7]
RP INTERACTION WITH TSG101, AND MASS SPECTROMETRY.
RX PubMed=18005716; DOI=10.1016/j.chom.2007.06.003;
RA Morita E., Sandrin V., Alam S.L., Eckert D.M., Gygi S.P.,
RA Sundquist W.I.;
RT "Identification of human MVB12 proteins as ESCRT-I subunits that
RT function in HIV budding.";
RL Cell Host Microbe 2:41-53(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, 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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
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 [11]
RP IDENTIFICATION IN AN ESCRT-I COMPLEX WITH UBAP1, AND SUBUNIT.
RX PubMed=21757351; DOI=10.1016/j.cub.2011.06.028;
RA Stefani F., Zhang L., Taylor S., Donovan J., Rollinson S., Doyotte A.,
RA Brownhill K., Bennion J., Pickering-Brown S., Woodman P.;
RT "UBAP1 is a component of an endosome-specific ESCRT-I complex that is
RT essential for MVB sorting.";
RL Curr. Biol. 21:1245-1250(2011).
RN [12]
RP TISSUE SPECIFICITY, VARIANT SPG53 ASN-382, AND CHARACTERIZATION OF
RP VARIANT SPG53 ASN-382.
RX PubMed=22717650; DOI=10.1136/jmedgenet-2012-100742;
RA Zivony-Elboum Y., Westbroek W., Kfir N., Savitzki D., Shoval Y.,
RA Bloom A., Rod R., Khayat M., Gross B., Samri W., Cohen H., Sonkin V.,
RA Freidman T., Geiger D., Fattal-Valevski A., Anikster Y., Waters A.M.,
RA Kleta R., Falik-Zaccai T.C.;
RT "A founder mutation in Vps37A causes autosomal recessive complex
RT hereditary spastic paraparesis.";
RL J. Med. Genet. 49:462-472(2012).
CC -!- FUNCTION: Component of the ESCRT-I complex, a regulator of
CC vesicular trafficking process. Required for the sorting of
CC endocytic ubiquitinated cargos into multivesicular bodies. May be
CC involved in cell growth and differentiation.
CC -!- SUBUNIT: Component of the ESCRT-I complex (endosomal sorting
CC complex required for transport I) which consists of TSG101, VPS28,
CC a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1
CC stoechiometry. Interacts with TSG101, VPS28 and HGS. Component of
CC an ESCRT-I complex (endosomal sorting complex required for
CC transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in
CC a 1:1:1:1 stoechiometry.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane; Peripheral membrane
CC protein. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8NEZ2-1; Sequence=Displayed;
CC Name=2; Synonyms=beta;
CC IsoId=Q8NEZ2-2; Sequence=VSP_025367;
CC Name=3;
CC IsoId=Q8NEZ2-3; Sequence=VSP_025368, VSP_025369;
CC -!- TISSUE SPECIFICITY: Widely expressed. Examined tissues include
CC heart, brain, placenta, liver, skeletal muscle, kidney and
CC pancreas. More abundant in liver. Strongly decreased or undetected
CC in hepatomas.
CC -!- DISEASE: Spastic paraplegia 53, autosomal recessive (SPG53)
CC [MIM:614898]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness
CC and spasticity of the lower limbs. Rate of progression and the
CC severity of symptoms are quite variable. Initial symptoms may
CC include difficulty with balance, weakness and stiffness in the
CC legs, muscle spasms, and dragging the toes when walking.
CC Complicated forms are characterized by the addition of such
CC neurological features as spastic quadriparesis, seizures,
CC dementia, amyotrophy, extrapyramidal disturbance, cerebral or
CC cerebellar atrophy, optic atrophy, and peripheral neuropathy, as
CC well as by extra neurological manifestations such as dysmorphism,
CC albinism, retinitis pigmentosa, deafness, dementia, amyotrophy and
CC ichthyosis. SPG53 is characterized by pronounced early onset
CC spastic paraparesis of upper and lower limbs, mild intellectual
CC disability, kyphosis, pectus carinatum and hypertrichosis.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the VPS37 family.
CC -!- SIMILARITY: Contains 1 VPS37 C-terminal domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH22363.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AY033079; AAK54349.1; -; mRNA.
DR EMBL; AF547097; AAQ12067.1; -; mRNA.
DR EMBL; AK057204; BAB71381.1; -; mRNA.
DR EMBL; AL834189; CAD38883.1; -; mRNA.
DR EMBL; BC022363; AAH22363.1; ALT_INIT; mRNA.
DR EMBL; BC067754; AAH67754.1; -; mRNA.
DR RefSeq; NP_001138624.1; NM_001145152.1.
DR RefSeq; NP_689628.2; NM_152415.2.
DR UniGene; Hs.343873; -.
DR ProteinModelPortal; Q8NEZ2; -.
DR IntAct; Q8NEZ2; 4.
DR MINT; MINT-2811404; -.
DR STRING; 9606.ENSP00000318629; -.
DR PhosphoSite; Q8NEZ2; -.
DR DMDM; 74715446; -.
DR PaxDb; Q8NEZ2; -.
DR PRIDE; Q8NEZ2; -.
DR DNASU; 137492; -.
DR Ensembl; ENST00000324815; ENSP00000318173; ENSG00000155975.
DR Ensembl; ENST00000324849; ENSP00000318629; ENSG00000155975.
DR Ensembl; ENST00000425020; ENSP00000412824; ENSG00000155975.
DR Ensembl; ENST00000521829; ENSP00000429680; ENSG00000155975.
DR GeneID; 137492; -.
DR KEGG; hsa:137492; -.
DR UCSC; uc003wxj.3; human.
DR CTD; 137492; -.
DR GeneCards; GC08P017149; -.
DR HGNC; HGNC:24928; VPS37A.
DR HPA; HPA024705; -.
DR HPA; HPA024781; -.
DR MIM; 609927; gene.
DR MIM; 614898; phenotype.
DR neXtProt; NX_Q8NEZ2; -.
DR Orphanet; 319199; Autosomal recessive spastic paraplegia type 53.
DR PharmGKB; PA142670615; -.
DR eggNOG; NOG243233; -.
DR HOGENOM; HOG000008031; -.
DR HOVERGEN; HBG054793; -.
DR InParanoid; Q8NEZ2; -.
DR KO; K12185; -.
DR OMA; PPYASQG; -.
DR OrthoDB; EOG7KQ22B; -.
DR PhylomeDB; Q8NEZ2; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; VPS37A; human.
DR GeneWiki; VPS37A; -.
DR GenomeRNAi; 137492; -.
DR NextBio; 83653; -.
DR PRO; PR:Q8NEZ2; -.
DR ArrayExpress; Q8NEZ2; -.
DR Bgee; Q8NEZ2; -.
DR CleanEx; HS_VPS37A; -.
DR Genevestigator; Q8NEZ2; -.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0000813; C:ESCRT I complex; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0008219; P:cell death; IEA:UniProtKB-KW.
DR GO; GO:0016197; P:endosomal transport; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IMP:UniProtKB.
DR GO; GO:0019082; P:viral protein processing; TAS:Reactome.
DR GO; GO:0019068; P:virion assembly; TAS:Reactome.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR009851; Mod_r.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF07200; Mod_r; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS51314; VPS37_C; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Disease mutation; Endosome;
KW Hereditary spastic paraplegia; Membrane; Neurodegeneration; Nucleus;
KW Phosphoprotein; Polymorphism; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1 397 Vacuolar protein sorting-associated
FT protein 37A.
FT /FTId=PRO_0000287198.
FT DOMAIN 308 397 VPS37 C-terminal.
FT MOD_RES 18 18 Phosphoserine.
FT VAR_SEQ 42 67 SIAEIQKDVEYRLPFTINNLTININI -> R (in
FT isoform 2).
FT /FTId=VSP_025367.
FT VAR_SEQ 140 185 LYSNPSGMSPYASQGFPFLPPYPPQEANRSITSLSVADTVS
FT SSTTS -> QLEIRWHHPHCLEISLARSSNSLGFSISSSIS
FT STRSKQEYHFFICC (in isoform 3).
FT /FTId=VSP_025368.
FT VAR_SEQ 186 397 Missing (in isoform 3).
FT /FTId=VSP_025369.
FT VARIANT 206 206 I -> F (in dbSNP:rs17502618).
FT /FTId=VAR_032287.
FT VARIANT 213 213 I -> V (in dbSNP:rs17687375).
FT /FTId=VAR_032288.
FT VARIANT 382 382 K -> N (in SPG53; found in patients with
FT complex hereditary spastic paraparesis;
FT hypomorphic mutation; does not affect
FT interaction with TSG101 and VPS28).
FT /FTId=VAR_068424.
FT CONFLICT 313 313 K -> R (in Ref. 2; BAB71381).
FT CONFLICT 324 324 S -> I (in Ref. 4; AAH67754).
SQ SEQUENCE 397 AA; 44314 MW; 96EBB670F04A0923 CRC64;
MSWLFPLTKS ASSSAAGSPG GLTSLQQQKQ RLIESLRNSH SSIAEIQKDV EYRLPFTINN
LTININILLP PQFPQEKPVI SVYPPIRHHL MDKQGVYVTS PLVNNFTMHS DLGKIIQSLL
DEFWKNPPVL APTSTAFPYL YSNPSGMSPY ASQGFPFLPP YPPQEANRSI TSLSVADTVS
SSTTSHTTAK PAAPSFGVLS NLPLPIPTVD ASIPTSQNGF GYKMPDVPDA FPELSELSVS
QLTDMNEQEE VLLEQFLTLP QLKQIITDKD DLVKSIEELA RKNLLLEPSL EAKRQTVLDK
YELLTQMKST FEKKMQRQHE LSESCSASAL QARLKVAAHE AEEESDNIAE DFLEGKMEID
DFLSSFMEKR TICHCRRAKE EKLQQAIAMH SQFHAPL
//
ID VP37A_HUMAN Reviewed; 397 AA.
AC Q8NEZ2; Q336D5; Q6NW27; Q8N3D7; Q8TBL7; Q96DL9;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2002, sequence version 1.
DT 22-JAN-2014, entry version 92.
DE RecName: Full=Vacuolar protein sorting-associated protein 37A;
DE Short=hVps37A;
DE AltName: Full=ESCRT-I complex subunit VPS37A;
DE AltName: Full=Hepatocellular carcinoma-related protein 1;
GN Name=VPS37A; Synonyms=HCRP1;
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] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=14623289; DOI=10.1016/j.bbrc.2003.10.109;
RA Xu Z., Liang L., Wang H., Li T., Zhao M.;
RT "HCRP1, a novel gene that is downregulated in hepatocellular
RT carcinoma, encodes a growth-inhibitory protein.";
RL Biochem. Biophys. Res. Commun. 311:1057-1066(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovium;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Prostate;
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 [5]
RP INTERACTION WITH TSG101.
RX PubMed=15218037; DOI=10.1074/jbc.M405226200;
RA Stuchell M.D., Garrus J.E., Mueller B., Stray K.M., Ghaffarian S.,
RA McKinnon R., Kraeusslich H.-G., Morham S.G., Sundquist W.I.;
RT "The human endosomal sorting complex required for transport (ESCRT-I)
RT and its role in HIV-1 budding.";
RL J. Biol. Chem. 279:36059-36071(2004).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TSG101; VPS28 AND
RP HGS.
RX PubMed=15240819; DOI=10.1091/mbc.E04-03-0250;
RA Bache K.G., Slagsvold T., Cabezas A., Rosendal K.R., Raiborg C.,
RA Stenmark H.;
RT "The growth-regulatory protein HCRP1/hVps37A is a subunit of mammalian
RT ESCRT-I and mediates receptor down-regulation.";
RL Mol. Biol. Cell 15:4337-4346(2004).
RN [7]
RP INTERACTION WITH TSG101, AND MASS SPECTROMETRY.
RX PubMed=18005716; DOI=10.1016/j.chom.2007.06.003;
RA Morita E., Sandrin V., Alam S.L., Eckert D.M., Gygi S.P.,
RA Sundquist W.I.;
RT "Identification of human MVB12 proteins as ESCRT-I subunits that
RT function in HIV budding.";
RL Cell Host Microbe 2:41-53(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, 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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
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 [11]
RP IDENTIFICATION IN AN ESCRT-I COMPLEX WITH UBAP1, AND SUBUNIT.
RX PubMed=21757351; DOI=10.1016/j.cub.2011.06.028;
RA Stefani F., Zhang L., Taylor S., Donovan J., Rollinson S., Doyotte A.,
RA Brownhill K., Bennion J., Pickering-Brown S., Woodman P.;
RT "UBAP1 is a component of an endosome-specific ESCRT-I complex that is
RT essential for MVB sorting.";
RL Curr. Biol. 21:1245-1250(2011).
RN [12]
RP TISSUE SPECIFICITY, VARIANT SPG53 ASN-382, AND CHARACTERIZATION OF
RP VARIANT SPG53 ASN-382.
RX PubMed=22717650; DOI=10.1136/jmedgenet-2012-100742;
RA Zivony-Elboum Y., Westbroek W., Kfir N., Savitzki D., Shoval Y.,
RA Bloom A., Rod R., Khayat M., Gross B., Samri W., Cohen H., Sonkin V.,
RA Freidman T., Geiger D., Fattal-Valevski A., Anikster Y., Waters A.M.,
RA Kleta R., Falik-Zaccai T.C.;
RT "A founder mutation in Vps37A causes autosomal recessive complex
RT hereditary spastic paraparesis.";
RL J. Med. Genet. 49:462-472(2012).
CC -!- FUNCTION: Component of the ESCRT-I complex, a regulator of
CC vesicular trafficking process. Required for the sorting of
CC endocytic ubiquitinated cargos into multivesicular bodies. May be
CC involved in cell growth and differentiation.
CC -!- SUBUNIT: Component of the ESCRT-I complex (endosomal sorting
CC complex required for transport I) which consists of TSG101, VPS28,
CC a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1
CC stoechiometry. Interacts with TSG101, VPS28 and HGS. Component of
CC an ESCRT-I complex (endosomal sorting complex required for
CC transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in
CC a 1:1:1:1 stoechiometry.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane; Peripheral membrane
CC protein. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8NEZ2-1; Sequence=Displayed;
CC Name=2; Synonyms=beta;
CC IsoId=Q8NEZ2-2; Sequence=VSP_025367;
CC Name=3;
CC IsoId=Q8NEZ2-3; Sequence=VSP_025368, VSP_025369;
CC -!- TISSUE SPECIFICITY: Widely expressed. Examined tissues include
CC heart, brain, placenta, liver, skeletal muscle, kidney and
CC pancreas. More abundant in liver. Strongly decreased or undetected
CC in hepatomas.
CC -!- DISEASE: Spastic paraplegia 53, autosomal recessive (SPG53)
CC [MIM:614898]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness
CC and spasticity of the lower limbs. Rate of progression and the
CC severity of symptoms are quite variable. Initial symptoms may
CC include difficulty with balance, weakness and stiffness in the
CC legs, muscle spasms, and dragging the toes when walking.
CC Complicated forms are characterized by the addition of such
CC neurological features as spastic quadriparesis, seizures,
CC dementia, amyotrophy, extrapyramidal disturbance, cerebral or
CC cerebellar atrophy, optic atrophy, and peripheral neuropathy, as
CC well as by extra neurological manifestations such as dysmorphism,
CC albinism, retinitis pigmentosa, deafness, dementia, amyotrophy and
CC ichthyosis. SPG53 is characterized by pronounced early onset
CC spastic paraparesis of upper and lower limbs, mild intellectual
CC disability, kyphosis, pectus carinatum and hypertrichosis.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the VPS37 family.
CC -!- SIMILARITY: Contains 1 VPS37 C-terminal domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH22363.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
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DR EMBL; AY033079; AAK54349.1; -; mRNA.
DR EMBL; AF547097; AAQ12067.1; -; mRNA.
DR EMBL; AK057204; BAB71381.1; -; mRNA.
DR EMBL; AL834189; CAD38883.1; -; mRNA.
DR EMBL; BC022363; AAH22363.1; ALT_INIT; mRNA.
DR EMBL; BC067754; AAH67754.1; -; mRNA.
DR RefSeq; NP_001138624.1; NM_001145152.1.
DR RefSeq; NP_689628.2; NM_152415.2.
DR UniGene; Hs.343873; -.
DR ProteinModelPortal; Q8NEZ2; -.
DR IntAct; Q8NEZ2; 4.
DR MINT; MINT-2811404; -.
DR STRING; 9606.ENSP00000318629; -.
DR PhosphoSite; Q8NEZ2; -.
DR DMDM; 74715446; -.
DR PaxDb; Q8NEZ2; -.
DR PRIDE; Q8NEZ2; -.
DR DNASU; 137492; -.
DR Ensembl; ENST00000324815; ENSP00000318173; ENSG00000155975.
DR Ensembl; ENST00000324849; ENSP00000318629; ENSG00000155975.
DR Ensembl; ENST00000425020; ENSP00000412824; ENSG00000155975.
DR Ensembl; ENST00000521829; ENSP00000429680; ENSG00000155975.
DR GeneID; 137492; -.
DR KEGG; hsa:137492; -.
DR UCSC; uc003wxj.3; human.
DR CTD; 137492; -.
DR GeneCards; GC08P017149; -.
DR HGNC; HGNC:24928; VPS37A.
DR HPA; HPA024705; -.
DR HPA; HPA024781; -.
DR MIM; 609927; gene.
DR MIM; 614898; phenotype.
DR neXtProt; NX_Q8NEZ2; -.
DR Orphanet; 319199; Autosomal recessive spastic paraplegia type 53.
DR PharmGKB; PA142670615; -.
DR eggNOG; NOG243233; -.
DR HOGENOM; HOG000008031; -.
DR HOVERGEN; HBG054793; -.
DR InParanoid; Q8NEZ2; -.
DR KO; K12185; -.
DR OMA; PPYASQG; -.
DR OrthoDB; EOG7KQ22B; -.
DR PhylomeDB; Q8NEZ2; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; VPS37A; human.
DR GeneWiki; VPS37A; -.
DR GenomeRNAi; 137492; -.
DR NextBio; 83653; -.
DR PRO; PR:Q8NEZ2; -.
DR ArrayExpress; Q8NEZ2; -.
DR Bgee; Q8NEZ2; -.
DR CleanEx; HS_VPS37A; -.
DR Genevestigator; Q8NEZ2; -.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0000813; C:ESCRT I complex; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0008219; P:cell death; IEA:UniProtKB-KW.
DR GO; GO:0016197; P:endosomal transport; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IMP:UniProtKB.
DR GO; GO:0019082; P:viral protein processing; TAS:Reactome.
DR GO; GO:0019068; P:virion assembly; TAS:Reactome.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR009851; Mod_r.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF07200; Mod_r; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS51314; VPS37_C; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Disease mutation; Endosome;
KW Hereditary spastic paraplegia; Membrane; Neurodegeneration; Nucleus;
KW Phosphoprotein; Polymorphism; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1 397 Vacuolar protein sorting-associated
FT protein 37A.
FT /FTId=PRO_0000287198.
FT DOMAIN 308 397 VPS37 C-terminal.
FT MOD_RES 18 18 Phosphoserine.
FT VAR_SEQ 42 67 SIAEIQKDVEYRLPFTINNLTININI -> R (in
FT isoform 2).
FT /FTId=VSP_025367.
FT VAR_SEQ 140 185 LYSNPSGMSPYASQGFPFLPPYPPQEANRSITSLSVADTVS
FT SSTTS -> QLEIRWHHPHCLEISLARSSNSLGFSISSSIS
FT STRSKQEYHFFICC (in isoform 3).
FT /FTId=VSP_025368.
FT VAR_SEQ 186 397 Missing (in isoform 3).
FT /FTId=VSP_025369.
FT VARIANT 206 206 I -> F (in dbSNP:rs17502618).
FT /FTId=VAR_032287.
FT VARIANT 213 213 I -> V (in dbSNP:rs17687375).
FT /FTId=VAR_032288.
FT VARIANT 382 382 K -> N (in SPG53; found in patients with
FT complex hereditary spastic paraparesis;
FT hypomorphic mutation; does not affect
FT interaction with TSG101 and VPS28).
FT /FTId=VAR_068424.
FT CONFLICT 313 313 K -> R (in Ref. 2; BAB71381).
FT CONFLICT 324 324 S -> I (in Ref. 4; AAH67754).
SQ SEQUENCE 397 AA; 44314 MW; 96EBB670F04A0923 CRC64;
MSWLFPLTKS ASSSAAGSPG GLTSLQQQKQ RLIESLRNSH SSIAEIQKDV EYRLPFTINN
LTININILLP PQFPQEKPVI SVYPPIRHHL MDKQGVYVTS PLVNNFTMHS DLGKIIQSLL
DEFWKNPPVL APTSTAFPYL YSNPSGMSPY ASQGFPFLPP YPPQEANRSI TSLSVADTVS
SSTTSHTTAK PAAPSFGVLS NLPLPIPTVD ASIPTSQNGF GYKMPDVPDA FPELSELSVS
QLTDMNEQEE VLLEQFLTLP QLKQIITDKD DLVKSIEELA RKNLLLEPSL EAKRQTVLDK
YELLTQMKST FEKKMQRQHE LSESCSASAL QARLKVAAHE AEEESDNIAE DFLEGKMEID
DFLSSFMEKR TICHCRRAKE EKLQQAIAMH SQFHAPL
//
MIM
609927
*RECORD*
*FIELD* NO
609927
*FIELD* TI
*609927 VACUOLAR PROTEIN SORTING 37, YEAST, HOMOLOG OF, A; VPS37A
;;HEPATOCELLULAR CARCINOMA-RELATED PROTEIN 1; HCRP1
read more*FIELD* TX
DESCRIPTION
The VPS37A gene encodes a subunit of the endosomal sorting complex
required for transport I (ESCRT-I) complex and also may play a role in
ubiquitination (summary by Zivony-Elboum et al., 2012).
CLONING
By positional cloning in the region of chromosome 8p21-p21 in which
deletions are frequently found in hepatocellular carcinoma (HCC), Xu et
al. (2003) identified a novel cDNA, which they designated HCRP1, from a
human liver cDNA library. HCRP1 encodes a deduced 397-amino acid
protein. Northern blot analysis showed ubiquitous expression of an
approximately 2-kb HCRP1 transcript, with most abundant expression in
liver. Western blot analysis showed reduced HCRP1 expression in 6 of 8
HCC tissues, but higher expression levels of HCRP1 in adjacent normal
tissues in all 8 cases. Transient transfection of GFP-HCRP1 fusion
constructs showed that HCRP1 is localized throughout the cell, but
predominantly in the nucleus.
By database analysis with the sequence of the yeast endosomal sorting
complex protein Vps37/Srn2 sequence as query, Bache et al. (2004)
identified HCRP1, which they designated VPS37A. The yeast and human
proteins share 22% sequence identity in the C terminus, and both contain
a modifier of rudimentary [mod(r)] domain.
By searching a database for sequences homologous to yeast Vps37,
Stuchell et al. (2004) identified VPS37A. VPS37A has an N-terminal
ubiquitin E2 variant (UEV) domain and a C-terminal mod(r) domain, and
both of these domains contain a coiled-coil region.
Zivony-Elboum et al. (2012) found expression of the VPS37 gene in
several human tissues, including heart, brain, placenta, lung, liver,
skeletal muscle, kidney, and pancreas, with lower levels of expression
in the brain and skeletal muscle.
GENE FUNCTION
Using a series of transfection experiments into HCC cell lines, Xu et
al. (2003) showed that overexpression of HCRP1 inhibits both
anchorage-dependent and anchorage-independent cell growth. Conversely,
reduction of HCRP1 expression by short hairpin RNA enhanced cell growth
and increased invasive ability in HCC cell lines.
Using immunofluorescence microscopy, Bache et al. (2004) demonstrated
colocalization of HCRP1 and VPS28 (601387) on LAMP1 (153330)-positive
endosomes. Immunoprecipitation experiments demonstrated strong
interaction of HCRP1 with TSG101 (601387) and VPS28, which are
components of the endosomal sorting complex required for transport I
(ESCRT-I), and weak interaction with HRS (604375), an upstream regulator
of the ESCRT-I complex. Pull-down assays demonstrated that the
interaction between HCRP1 and TSG101 occurs through the mod(r) domain.
By size exclusion chromatography, HCRP1 cofractionated with TSG101 and
VPS28. Depletion of TSG101 by siRNA treatment resulted in reduction in
HCRP1 levels in HeLa cells. Whereas siRNA-mediated depletion of HCRP1
had no effect on either TSG101 or VPS28 levels, it strongly retarded EGF
receptor (131550) degradation.
MAPPING
Xu et al. (2003) identified the VPS37A gene within the region of
frequent loss of heterozygosity in HCC on chromosome 8p23-p21.
MOLECULAR GENETICS
In 9 affected members of 2 consanguineous Arab Moslem families with
early-onset autosomal recessive spastic paraplegia-53 (SPG53; 614898),
Zivony-Elboum et al. (2012) identified a homozygous mutation in the
VPS37A gene (K382N; 609927.0001). The mutation was found by linkage
analysis followed by candidate gene sequencing. Although the mutant
protein was expressed at normal levels in patient cells and showed
normal interaction with TSG101, knockdown of the corresponding gene in
zebrafish caused motility defects. Zivony-Elboum et al. (2012)
postulated that the disorder may result from defects in vesicular
trafficking or ubiquitination.
ANIMAL MODEL
Zivony-Elboum et al. (2012) found that morpholino knockdown of Vps37a in
zebrafish embryos resulted in a significant loss of motility.
*FIELD* AV
.0001
SPASTIC PARAPLEGIA 53, AUTOSOMAL RECESSIVE
VPS37A, LYS382ASN
In 9 affected members of 2 consanguineous Arab Moslem families with
autosomal recessive spastic paraplegia-53 (SPG53; 614898), Zivony-Elboum
et al. (2012) identified a homozygous 1146A-T transition in exon 11 of
the VPS37A gene, resulting in a lys382-to-asn (K382N) substitution at a
highly conserved residue in the C terminus. The mutation was found by
linkage analysis followed by candidate gene sequencing. Haplotype
analysis indicated a founder effect. The mutation was not found in
several large databases or in 428 matched control chromosomes, but was
found in the heterozygous state in 3 of 50 residents of the same
village, again indicating a founder effect. Patient cells showed normal
levels of mutant VPS37A mRNA and protein, and the mutant protein showed
normal interaction with TSG101 (601387), suggesting that the mutation
does not destabilize the endosomal sorting complex required for
transport I (ESCRT-I).
*FIELD* RF
1. Bache, K. G.; Slagsvold, T.; Cabezas, A.; Rosendal, K. R.; Raiborg,
C.; Stenmark, H.: The growth-regulatory protein HCRP1/hVps37A is
a subunit of mammalian ESCRT-I and mediates receptor down-regulation. Molec.
Biol. Cell 15: 4337-4346, 2004.
2. Stuchell, M. D.; Garrus, J. E.; Muller, B.; Stray, K. M.; Ghaffarian,
S.; McKinnon, R.; Krausslich, H.-G.; Morham, S. G.; Sundquist, W.
I.: The human endosomal sorting complex required for transport (ESCRT-I)
and its role in HIV-1 budding. J. Biol. Chem. 279: 36059-36071,
2004.
3. Xu, Z.; Liang, L.; Wang, H.; Li, T.; Zhao, M.: HCRP1, a novel
gene that is downregulated in hepatocellular carcinoma, encodes a
growth-inhibitory protein. Biochem. Biophys. Res. Commun. 311: 1057-1066,
2003.
4. Zivony-Elboum, Y.; Westbroek, W.; Kfir, N.; Savitzki, D.; Shoval,
Y.; Bloom, A.; Rod, R.; Khayat, M.; Gross, B.; Samri, W.; Cohen, H.;
Sonkin, V.; Freidman, T.; Geiger, D.; Fattal-Valevski, A.; Anikster,
Y.; Waters, A. M.; Kleta, R.; Falik-Zaccai, T. C.: A founder mutation
in Vps37A causes autosomal recessive complex hereditary spastic paraparesis. J.
Med. Genet. 49: 462-472, 2012.
*FIELD* CN
Cassandra L. Kniffin - updated: 10/25/2012
Patricia A. Hartz - updated: 4/4/2006
*FIELD* CD
Laura L. Baxter: 2/24/2006
*FIELD* ED
carol: 11/01/2012
ckniffin: 10/25/2012
mgross: 4/14/2008
mgross: 4/10/2006
terry: 4/4/2006
carol: 2/24/2006
*RECORD*
*FIELD* NO
609927
*FIELD* TI
*609927 VACUOLAR PROTEIN SORTING 37, YEAST, HOMOLOG OF, A; VPS37A
;;HEPATOCELLULAR CARCINOMA-RELATED PROTEIN 1; HCRP1
read more*FIELD* TX
DESCRIPTION
The VPS37A gene encodes a subunit of the endosomal sorting complex
required for transport I (ESCRT-I) complex and also may play a role in
ubiquitination (summary by Zivony-Elboum et al., 2012).
CLONING
By positional cloning in the region of chromosome 8p21-p21 in which
deletions are frequently found in hepatocellular carcinoma (HCC), Xu et
al. (2003) identified a novel cDNA, which they designated HCRP1, from a
human liver cDNA library. HCRP1 encodes a deduced 397-amino acid
protein. Northern blot analysis showed ubiquitous expression of an
approximately 2-kb HCRP1 transcript, with most abundant expression in
liver. Western blot analysis showed reduced HCRP1 expression in 6 of 8
HCC tissues, but higher expression levels of HCRP1 in adjacent normal
tissues in all 8 cases. Transient transfection of GFP-HCRP1 fusion
constructs showed that HCRP1 is localized throughout the cell, but
predominantly in the nucleus.
By database analysis with the sequence of the yeast endosomal sorting
complex protein Vps37/Srn2 sequence as query, Bache et al. (2004)
identified HCRP1, which they designated VPS37A. The yeast and human
proteins share 22% sequence identity in the C terminus, and both contain
a modifier of rudimentary [mod(r)] domain.
By searching a database for sequences homologous to yeast Vps37,
Stuchell et al. (2004) identified VPS37A. VPS37A has an N-terminal
ubiquitin E2 variant (UEV) domain and a C-terminal mod(r) domain, and
both of these domains contain a coiled-coil region.
Zivony-Elboum et al. (2012) found expression of the VPS37 gene in
several human tissues, including heart, brain, placenta, lung, liver,
skeletal muscle, kidney, and pancreas, with lower levels of expression
in the brain and skeletal muscle.
GENE FUNCTION
Using a series of transfection experiments into HCC cell lines, Xu et
al. (2003) showed that overexpression of HCRP1 inhibits both
anchorage-dependent and anchorage-independent cell growth. Conversely,
reduction of HCRP1 expression by short hairpin RNA enhanced cell growth
and increased invasive ability in HCC cell lines.
Using immunofluorescence microscopy, Bache et al. (2004) demonstrated
colocalization of HCRP1 and VPS28 (601387) on LAMP1 (153330)-positive
endosomes. Immunoprecipitation experiments demonstrated strong
interaction of HCRP1 with TSG101 (601387) and VPS28, which are
components of the endosomal sorting complex required for transport I
(ESCRT-I), and weak interaction with HRS (604375), an upstream regulator
of the ESCRT-I complex. Pull-down assays demonstrated that the
interaction between HCRP1 and TSG101 occurs through the mod(r) domain.
By size exclusion chromatography, HCRP1 cofractionated with TSG101 and
VPS28. Depletion of TSG101 by siRNA treatment resulted in reduction in
HCRP1 levels in HeLa cells. Whereas siRNA-mediated depletion of HCRP1
had no effect on either TSG101 or VPS28 levels, it strongly retarded EGF
receptor (131550) degradation.
MAPPING
Xu et al. (2003) identified the VPS37A gene within the region of
frequent loss of heterozygosity in HCC on chromosome 8p23-p21.
MOLECULAR GENETICS
In 9 affected members of 2 consanguineous Arab Moslem families with
early-onset autosomal recessive spastic paraplegia-53 (SPG53; 614898),
Zivony-Elboum et al. (2012) identified a homozygous mutation in the
VPS37A gene (K382N; 609927.0001). The mutation was found by linkage
analysis followed by candidate gene sequencing. Although the mutant
protein was expressed at normal levels in patient cells and showed
normal interaction with TSG101, knockdown of the corresponding gene in
zebrafish caused motility defects. Zivony-Elboum et al. (2012)
postulated that the disorder may result from defects in vesicular
trafficking or ubiquitination.
ANIMAL MODEL
Zivony-Elboum et al. (2012) found that morpholino knockdown of Vps37a in
zebrafish embryos resulted in a significant loss of motility.
*FIELD* AV
.0001
SPASTIC PARAPLEGIA 53, AUTOSOMAL RECESSIVE
VPS37A, LYS382ASN
In 9 affected members of 2 consanguineous Arab Moslem families with
autosomal recessive spastic paraplegia-53 (SPG53; 614898), Zivony-Elboum
et al. (2012) identified a homozygous 1146A-T transition in exon 11 of
the VPS37A gene, resulting in a lys382-to-asn (K382N) substitution at a
highly conserved residue in the C terminus. The mutation was found by
linkage analysis followed by candidate gene sequencing. Haplotype
analysis indicated a founder effect. The mutation was not found in
several large databases or in 428 matched control chromosomes, but was
found in the heterozygous state in 3 of 50 residents of the same
village, again indicating a founder effect. Patient cells showed normal
levels of mutant VPS37A mRNA and protein, and the mutant protein showed
normal interaction with TSG101 (601387), suggesting that the mutation
does not destabilize the endosomal sorting complex required for
transport I (ESCRT-I).
*FIELD* RF
1. Bache, K. G.; Slagsvold, T.; Cabezas, A.; Rosendal, K. R.; Raiborg,
C.; Stenmark, H.: The growth-regulatory protein HCRP1/hVps37A is
a subunit of mammalian ESCRT-I and mediates receptor down-regulation. Molec.
Biol. Cell 15: 4337-4346, 2004.
2. Stuchell, M. D.; Garrus, J. E.; Muller, B.; Stray, K. M.; Ghaffarian,
S.; McKinnon, R.; Krausslich, H.-G.; Morham, S. G.; Sundquist, W.
I.: The human endosomal sorting complex required for transport (ESCRT-I)
and its role in HIV-1 budding. J. Biol. Chem. 279: 36059-36071,
2004.
3. Xu, Z.; Liang, L.; Wang, H.; Li, T.; Zhao, M.: HCRP1, a novel
gene that is downregulated in hepatocellular carcinoma, encodes a
growth-inhibitory protein. Biochem. Biophys. Res. Commun. 311: 1057-1066,
2003.
4. Zivony-Elboum, Y.; Westbroek, W.; Kfir, N.; Savitzki, D.; Shoval,
Y.; Bloom, A.; Rod, R.; Khayat, M.; Gross, B.; Samri, W.; Cohen, H.;
Sonkin, V.; Freidman, T.; Geiger, D.; Fattal-Valevski, A.; Anikster,
Y.; Waters, A. M.; Kleta, R.; Falik-Zaccai, T. C.: A founder mutation
in Vps37A causes autosomal recessive complex hereditary spastic paraparesis. J.
Med. Genet. 49: 462-472, 2012.
*FIELD* CN
Cassandra L. Kniffin - updated: 10/25/2012
Patricia A. Hartz - updated: 4/4/2006
*FIELD* CD
Laura L. Baxter: 2/24/2006
*FIELD* ED
carol: 11/01/2012
ckniffin: 10/25/2012
mgross: 4/14/2008
mgross: 4/10/2006
terry: 4/4/2006
carol: 2/24/2006
MIM
614898
*RECORD*
*FIELD* NO
614898
*FIELD* TI
#614898 SPASTIC PARAPLEGIA 53, AUTOSOMAL RECESSIVE; SPG53
*FIELD* TX
A number sign (#) is used with this entry because autosomal recessive
read morespastic paraplegia-53 (SPG53) can be caused by homozygous mutation in
the VPS37A gene (609927) on chromosome 8p22.
DESCRIPTION
SPG53 is an autosomal recessive neurologic disorder characterized by
onset in infancy of delayed motor development progressing to upper and
lower limb spasticity with impaired walking. Affected individuals also
show mild to moderate cognitive impairment (summary by Zivony-Elboum et
al., 2012).
CLINICAL FEATURES
Zivony-Elboum et al. (2012) reported 9 patients from 2 Arab Moslem
families with early-onset spastic paraplegia. Affected individuals
showed developmental and motor delay during the first 2 years of life.
They had unsteadiness in standing and difficulty walking. All affected
children presented with spasticity in the lower limbs that progressed to
the upper extremities, requiring recurrent physiotherapy and ligament
lengthening operations. Marked kyphosis was noted in all patients, and
some had pectus carinatum. Some patients regained the ability to walk
with aid after botulinum injections. All had mild to moderate cognitive
and speech delay. Three patients had hypertrichosis, and 3 had mildly
impaired vibration or position sense.
INHERITANCE
The transmission pattern in the families with SPG53 reported by
Zivony-Elboum et al. (2012) was consistent with autosomal recessive
inheritance.
MAPPING
By genomewide linkage analysis of a large consanguineous Arab Muslim
family with SPG53, Zivony-Elboum et al. (2012) found linkage to a 12-Mb
region on chromosome 8p22 between D8S550 and D8S1734 (maximum lod score
of 6.7 at D8S261).
MOLECULAR GENETICS
By linkage analysis followed by candidate gene sequencing, Zivony-Elboum
et al. (2012) identified a homozygous mutation in the VPS37A gene
(K382N; 609927) in affected members of 2 families with SPG53. Although
the mutant protein was expressed at normal levels in patient cells and
showed normal interaction with TSG101 (601387), knockdown of the
corresponding gene in zebrafish caused motility defects. Zivony-Elboum
et al. (2012) postulated that the disorder may result from defects in
vesicular trafficking or ubiquitination.
*FIELD* RF
1. Zivony-Elboum, Y.; Westbroek, W.; Kfir, N.; Savitzki, D.; Shoval,
Y.; Bloom, A.; Rod, R.; Khayat, M.; Gross, B.; Samri, W.; Cohen, H.;
Sonkin, V.; Freidman, T.; Geiger, D.; Fattal-Valevski, A.; Anikster,
Y.; Waters, A. M.; Kleta, R.; Falik-Zaccai, T. C.: A founder mutation
in Vps37A causes autosomal recessive complex hereditary spastic paraparesis. J.
Med. Genet. 49: 462-472, 2012.
*FIELD* CS
INHERITANCE:
Autosomal recessive
CHEST:
[External features];
Pectus carinatum (in some)
SKELETAL:
[Spine];
Kyphosis
SKIN, NAILS, HAIR:
[Hair];
Hypertrichosis (in 3 patients)
MUSCLE, SOFT TISSUE:
Increased muscle tone
NEUROLOGIC:
[Central nervous system];
Delayed psychomotor development;
Unsteady standing;
Gait difficulties;
Cognitive impairment, mild to moderate;
Delayed speech;
Spasticity, upper and lower limbs;
Hyperreflexia;
Clonus;
Dystonia (in 2 patients);
[Peripheral nervous system];
Decreased vibration or position sense (in 3 patients)
MISCELLANEOUS:
Onset in the first 2 years of life;
Two Arab Muslim families have been reported (last curated October
2012)
MOLECULAR BASIS:
Caused by mutation in the homolog of the yeast vacuolar protein sorting
37 gene (VPS37A, 609927.0001)
*FIELD* CD
Cassandra L. Kniffin: 10/25/2012
*FIELD* ED
joanna: 11/13/2012
ckniffin: 10/25/2012
*FIELD* CD
Cassandra L. Kniffin: 10/25/2012
*FIELD* ED
carol: 11/01/2012
terry: 10/26/2012
ckniffin: 10/25/2012
*RECORD*
*FIELD* NO
614898
*FIELD* TI
#614898 SPASTIC PARAPLEGIA 53, AUTOSOMAL RECESSIVE; SPG53
*FIELD* TX
A number sign (#) is used with this entry because autosomal recessive
read morespastic paraplegia-53 (SPG53) can be caused by homozygous mutation in
the VPS37A gene (609927) on chromosome 8p22.
DESCRIPTION
SPG53 is an autosomal recessive neurologic disorder characterized by
onset in infancy of delayed motor development progressing to upper and
lower limb spasticity with impaired walking. Affected individuals also
show mild to moderate cognitive impairment (summary by Zivony-Elboum et
al., 2012).
CLINICAL FEATURES
Zivony-Elboum et al. (2012) reported 9 patients from 2 Arab Moslem
families with early-onset spastic paraplegia. Affected individuals
showed developmental and motor delay during the first 2 years of life.
They had unsteadiness in standing and difficulty walking. All affected
children presented with spasticity in the lower limbs that progressed to
the upper extremities, requiring recurrent physiotherapy and ligament
lengthening operations. Marked kyphosis was noted in all patients, and
some had pectus carinatum. Some patients regained the ability to walk
with aid after botulinum injections. All had mild to moderate cognitive
and speech delay. Three patients had hypertrichosis, and 3 had mildly
impaired vibration or position sense.
INHERITANCE
The transmission pattern in the families with SPG53 reported by
Zivony-Elboum et al. (2012) was consistent with autosomal recessive
inheritance.
MAPPING
By genomewide linkage analysis of a large consanguineous Arab Muslim
family with SPG53, Zivony-Elboum et al. (2012) found linkage to a 12-Mb
region on chromosome 8p22 between D8S550 and D8S1734 (maximum lod score
of 6.7 at D8S261).
MOLECULAR GENETICS
By linkage analysis followed by candidate gene sequencing, Zivony-Elboum
et al. (2012) identified a homozygous mutation in the VPS37A gene
(K382N; 609927) in affected members of 2 families with SPG53. Although
the mutant protein was expressed at normal levels in patient cells and
showed normal interaction with TSG101 (601387), knockdown of the
corresponding gene in zebrafish caused motility defects. Zivony-Elboum
et al. (2012) postulated that the disorder may result from defects in
vesicular trafficking or ubiquitination.
*FIELD* RF
1. Zivony-Elboum, Y.; Westbroek, W.; Kfir, N.; Savitzki, D.; Shoval,
Y.; Bloom, A.; Rod, R.; Khayat, M.; Gross, B.; Samri, W.; Cohen, H.;
Sonkin, V.; Freidman, T.; Geiger, D.; Fattal-Valevski, A.; Anikster,
Y.; Waters, A. M.; Kleta, R.; Falik-Zaccai, T. C.: A founder mutation
in Vps37A causes autosomal recessive complex hereditary spastic paraparesis. J.
Med. Genet. 49: 462-472, 2012.
*FIELD* CS
INHERITANCE:
Autosomal recessive
CHEST:
[External features];
Pectus carinatum (in some)
SKELETAL:
[Spine];
Kyphosis
SKIN, NAILS, HAIR:
[Hair];
Hypertrichosis (in 3 patients)
MUSCLE, SOFT TISSUE:
Increased muscle tone
NEUROLOGIC:
[Central nervous system];
Delayed psychomotor development;
Unsteady standing;
Gait difficulties;
Cognitive impairment, mild to moderate;
Delayed speech;
Spasticity, upper and lower limbs;
Hyperreflexia;
Clonus;
Dystonia (in 2 patients);
[Peripheral nervous system];
Decreased vibration or position sense (in 3 patients)
MISCELLANEOUS:
Onset in the first 2 years of life;
Two Arab Muslim families have been reported (last curated October
2012)
MOLECULAR BASIS:
Caused by mutation in the homolog of the yeast vacuolar protein sorting
37 gene (VPS37A, 609927.0001)
*FIELD* CD
Cassandra L. Kniffin: 10/25/2012
*FIELD* ED
joanna: 11/13/2012
ckniffin: 10/25/2012
*FIELD* CD
Cassandra L. Kniffin: 10/25/2012
*FIELD* ED
carol: 11/01/2012
terry: 10/26/2012
ckniffin: 10/25/2012