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Q8NEZ2 (VP37A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 95. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Vacuolar protein sorting-associated protein 37A

Short name=hVps37A
Alternative name(s):
ESCRT-I complex subunit VPS37A
Hepatocellular carcinoma-related protein 1
Gene names
Name:VPS37A
Synonyms:HCRP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length397 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in cell growth and differentiation. Ref.6

Subunit structure

Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoechiometry. Interacts with TSG101, VPS28 and HGS. Component of an ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 stoechiometry. Ref.5 Ref.6 Ref.7 Ref.11

Subcellular location

Late endosome membrane; Peripheral membrane protein. Nucleus Ref.1 Ref.6.

Tissue specificity

Widely expressed. Examined tissues include heart, brain, placenta, liver, skeletal muscle, kidney and pancreas. More abundant in liver. Strongly decreased or undetected in hepatomas. Ref.1 Ref.12

Involvement in disease

Spastic paraplegia 53, autosomal recessive (SPG53) [MIM:614898]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. SPG53 is characterized by pronounced early onset spastic paraparesis of upper and lower limbs, mild intellectual disability, kyphosis, pectus carinatum and hypertrichosis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

Sequence similarities

Belongs to the VPS37 family.

Contains 1 VPS37 C-terminal domain.

Sequence caution

The sequence AAH22363.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processProtein transport
Transport
   Cellular componentEndosome
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Hereditary spastic paraplegia
Neurodegeneration
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell death

Inferred from electronic annotation. Source: UniProtKB-KW

endosomal transport

Traceable author statement. Source: Reactome

intracellular transport of virus

Traceable author statement. Source: Reactome

membrane organization

Traceable author statement. Source: Reactome

protein transport

Inferred from electronic annotation. Source: UniProtKB-KW

ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway

Inferred from mutant phenotype Ref.11. Source: UniProtKB

viral life cycle

Traceable author statement. Source: Reactome

viral process

Traceable author statement. Source: Reactome

viral protein processing

Traceable author statement. Source: Reactome

virion assembly

Traceable author statement. Source: Reactome

   Cellular_componentESCRT I complex

Inferred from direct assay Ref.11. Source: UniProtKB

centrosome

Inferred from direct assay. Source: HPA

cytoplasm

Inferred from direct assay. Source: HPA

endosome membrane

Traceable author statement. Source: Reactome

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

late endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay. Source: HPA

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8NEZ2-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8NEZ2-2)

Also known as: beta;

The sequence of this isoform differs from the canonical sequence as follows:
     42-67: SIAEIQKDVEYRLPFTINNLTININI → R
Isoform 3 (identifier: Q8NEZ2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     140-185: LYSNPSGMSP...ADTVSSSTTS → QLEIRWHHPH...KQEYHFFICC
     186-397: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 397397Vacuolar protein sorting-associated protein 37A
PRO_0000287198

Regions

Domain308 – 39790VPS37 C-terminal

Amino acid modifications

Modified residue181Phosphoserine Ref.8

Natural variations

Alternative sequence42 – 6726SIAEI…ININI → R in isoform 2.
VSP_025367
Alternative sequence140 – 18546LYSNP…SSTTS → QLEIRWHHPHCLEISLARSS NSLGFSISSSISSTRSKQEY HFFICC in isoform 3.
VSP_025368
Alternative sequence186 – 397212Missing in isoform 3.
VSP_025369
Natural variant2061I → F.
Corresponds to variant rs17502618 [ dbSNP | Ensembl ].
VAR_032287
Natural variant2131I → V.
Corresponds to variant rs17687375 [ dbSNP | Ensembl ].
VAR_032288
Natural variant3821K → N in SPG53; found in patients with complex hereditary spastic paraparesis; hypomorphic mutation; does not affect interaction with TSG101 and VPS28. Ref.12
VAR_068424

Experimental info

Sequence conflict3131K → R in BAB71381. Ref.2
Sequence conflict3241S → I in AAH67754. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 96EBB670F04A0923

FASTA39744,314
        10         20         30         40         50         60 
MSWLFPLTKS ASSSAAGSPG GLTSLQQQKQ RLIESLRNSH SSIAEIQKDV EYRLPFTINN 

        70         80         90        100        110        120 
LTININILLP PQFPQEKPVI SVYPPIRHHL MDKQGVYVTS PLVNNFTMHS DLGKIIQSLL 

       130        140        150        160        170        180 
DEFWKNPPVL APTSTAFPYL YSNPSGMSPY ASQGFPFLPP YPPQEANRSI TSLSVADTVS 

       190        200        210        220        230        240 
SSTTSHTTAK PAAPSFGVLS NLPLPIPTVD ASIPTSQNGF GYKMPDVPDA FPELSELSVS 

       250        260        270        280        290        300 
QLTDMNEQEE VLLEQFLTLP QLKQIITDKD DLVKSIEELA RKNLLLEPSL EAKRQTVLDK 

       310        320        330        340        350        360 
YELLTQMKST FEKKMQRQHE LSESCSASAL QARLKVAAHE AEEESDNIAE DFLEGKMEID 

       370        380        390 
DFLSSFMEKR TICHCRRAKE EKLQQAIAMH SQFHAPL 

« Hide

Isoform 2 (beta) [UniParc].

Checksum: C0793CE39FC71A49
Show »

FASTA37241,456
Isoform 3 [UniParc].

Checksum: AF11A1206F0BCA95
Show »

FASTA18520,891

References

« Hide 'large scale' references
[1]"HCRP1, a novel gene that is downregulated in hepatocellular carcinoma, encodes a growth-inhibitory protein."
Xu Z., Liang L., Wang H., Li T., Zhao M.
Biochem. Biophys. Res. Commun. 311:1057-1066(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Liver.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Synovium.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Melanoma.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain and Prostate.
[5]"The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding."
Stuchell M.D., Garrus J.E., Mueller B., Stray K.M., Ghaffarian S., McKinnon R., Kraeusslich H.-G., Morham S.G., Sundquist W.I.
J. Biol. Chem. 279:36059-36071(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TSG101.
[6]"The growth-regulatory protein HCRP1/hVps37A is a subunit of mammalian ESCRT-I and mediates receptor down-regulation."
Bache K.G., Slagsvold T., Cabezas A., Rosendal K.R., Raiborg C., Stenmark H.
Mol. Biol. Cell 15:4337-4346(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TSG101; VPS28 AND HGS.
[7]"Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding."
Morita E., Sandrin V., Alam S.L., Eckert D.M., Gygi S.P., Sundquist W.I.
Cell Host Microbe 2:41-53(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TSG101, IDENTIFICATION BY MASS SPECTROMETRY.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting."
Stefani F., Zhang L., Taylor S., Donovan J., Rollinson S., Doyotte A., Brownhill K., Bennion J., Pickering-Brown S., Woodman P.
Curr. Biol. 21:1245-1250(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN AN ESCRT-I COMPLEX WITH UBAP1, SUBUNIT.
[12]"A founder mutation in Vps37A causes autosomal recessive complex hereditary spastic paraparesis."
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.
J. Med. Genet. 49:462-472(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, VARIANT SPG53 ASN-382, CHARACTERIZATION OF VARIANT SPG53 ASN-382.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY033079 mRNA. Translation: AAK54349.1.
AF547097 mRNA. Translation: AAQ12067.1.
AK057204 mRNA. Translation: BAB71381.1.
AL834189 mRNA. Translation: CAD38883.1.
BC022363 mRNA. Translation: AAH22363.1. Different initiation.
BC067754 mRNA. Translation: AAH67754.1.
RefSeqNP_001138624.1. NM_001145152.1.
NP_689628.2. NM_152415.2.
UniGeneHs.343873.

3D structure databases

ProteinModelPortalQ8NEZ2.
SMRQ8NEZ2. Positions 63-124, 321-380.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid126479. 12 interactions.
IntActQ8NEZ2. 4 interactions.
MINTMINT-2811404.
STRING9606.ENSP00000318629.

PTM databases

PhosphoSiteQ8NEZ2.

Polymorphism databases

DMDM74715446.

Proteomic databases

PaxDbQ8NEZ2.
PRIDEQ8NEZ2.

Protocols and materials databases

DNASU137492.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000324815; ENSP00000318173; ENSG00000155975. [Q8NEZ2-3]
ENST00000324849; ENSP00000318629; ENSG00000155975. [Q8NEZ2-1]
ENST00000425020; ENSP00000412824; ENSG00000155975. [Q8NEZ2-3]
ENST00000521829; ENSP00000429680; ENSG00000155975. [Q8NEZ2-2]
GeneID137492.
KEGGhsa:137492.
UCSCuc003wxj.3. human. [Q8NEZ2-1]
uc003wxk.3. human. [Q8NEZ2-2]

Organism-specific databases

CTD137492.
GeneCardsGC08P017149.
HGNCHGNC:24928. VPS37A.
HPAHPA024705.
HPA024781.
MIM609927. gene.
614898. phenotype.
neXtProtNX_Q8NEZ2.
Orphanet319199. Autosomal recessive spastic paraplegia type 53.
PharmGKBPA142670615.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG243233.
HOGENOMHOG000008031.
HOVERGENHBG054793.
InParanoidQ8NEZ2.
KOK12185.
OMAPPYASQG.
OrthoDBEOG7KQ22B.
PhylomeDBQ8NEZ2.
TreeFamTF332146.

Enzyme and pathway databases

ReactomeREACT_11123. Membrane Trafficking.
REACT_116125. Disease.

Gene expression databases

ArrayExpressQ8NEZ2.
BgeeQ8NEZ2.
CleanExHS_VPS37A.
GenevestigatorQ8NEZ2.

Family and domain databases

Gene3D3.10.110.10. 1 hit.
InterProIPR009851. Mod_r.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamPF07200. Mod_r. 1 hit.
[Graphical view]
SUPFAMSSF54495. SSF54495. 1 hit.
PROSITEPS51314. VPS37_C. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSVPS37A. human.
GeneWikiVPS37A.
GenomeRNAi137492.
NextBio83653.
PROQ8NEZ2.
SOURCESearch...

Entry information

Entry nameVP37A_HUMAN
AccessionPrimary (citable) accession number: Q8NEZ2
Secondary accession number(s): Q336D5 expand/collapse secondary AC list , Q6NW27, Q8N3D7, Q8TBL7, Q96DL9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: October 1, 2002
Last modified: April 16, 2014
This is version 95 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM