Q8NEZ2 (VP37A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	397 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.5 Ref.6 Ref.7
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.10
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 characterized by the addition of such neurological features as spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations such as dysmorphism, albinism, retinitis pigmentosa, deafness, dementia, amyotrophy and ichthyosis. 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.
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 process	Protein transport Transport
Cellular component	Endosome Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Hereditary spastic paraplegia Neurodegeneration
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW cellular membrane organization Traceable author statement. Source: Reactome egress of virus within host cell Traceable author statement. Source: Reactome endosomal transport Traceable author statement. Source: Reactome protein transport Inferred from electronic annotation. Source: UniProtKB-KW viral protein processing Traceable author statement. Source: Reactome virion assembly Traceable author statement. Source: Reactome
Cellular_component	centrosome Inferred from direct assay. Source: HPA endosome membrane Traceable author statement. Source: Reactome 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 397	397	Vacuolar protein sorting-associated protein 37A		PRO_0000287198
Regions
	Domain	308 – 397	90	VPS37 C-terminal
Amino acid modifications
	Modified residue	18	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	42 – 67	26	SIAEI…ININI → R in isoform 2.		VSP_025367
	Alternative sequence	140 – 185	46	LYSNP…SSTTS → QLEIRWHHPHCLEISLARSS NSLGFSISSSISSTRSKQEY HFFICC in isoform 3.		VSP_025368
	Alternative sequence	186 – 397	212	Missing in isoform 3.		VSP_025369
	Natural variant	206	1	I → F. Corresponds to variant rs17502618 [ dbSNP | Ensembl ].		VAR_032287
	Natural variant	213	1	I → V. Corresponds to variant rs17687375 [ dbSNP | Ensembl ].		VAR_032288
	Natural variant	382	1	K → N in SPG53; found in patients with complex hereditary spastic paraparesis; hypomorphic mutation; does not affect interaction with TSG101 and VPS28. Ref.10		VAR_068424
Experimental info
	Sequence conflict	313	1	K → R in BAB71381. Ref.2
	Sequence conflict	324	1	S → I in AAH67754. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 96EBB670F04A0923	FASTA	397	44,314
	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
	Isoform 2 (beta) [UniParc]. Checksum: C0793CE39FC71A49	FASTA	372	41,456
	10 20 30 40 50 60 MSWLFPLTKS ASSSAAGSPG GLTSLQQQKQ RLIESLRNSH SRLLPPQFPQ EKPVISVYPP 70 80 90 100 110 120 IRHHLMDKQG VYVTSPLVNN FTMHSDLGKI IQSLLDEFWK NPPVLAPTST AFPYLYSNPS 130 140 150 160 170 180 GMSPYASQGF PFLPPYPPQE ANRSITSLSV ADTVSSSTTS HTTAKPAAPS FGVLSNLPLP 190 200 210 220 230 240 IPTVDASIPT SQNGFGYKMP DVPDAFPELS ELSVSQLTDM NEQEEVLLEQ FLTLPQLKQI 250 260 270 280 290 300 ITDKDDLVKS IEELARKNLL LEPSLEAKRQ TVLDKYELLT QMKSTFEKKM QRQHELSESC 310 320 330 340 350 360 SASALQARLK VAAHEAEEES DNIAEDFLEG KMEIDDFLSS FMEKRTICHC RRAKEEKLQQ 370 AIAMHSQFHA PL
	Isoform 3 [UniParc]. Checksum: AF11A1206F0BCA95	FASTA	185	20,891
	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 APTSTAFPYQ LEIRWHHPHC LEISLARSSN SLGFSISSSI SSTRSKQEYH FFICC

References

	« Hide 'large scale' referencesShow '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. , 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, 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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].
[10]	"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.
IPI	IPI00166536. IPI00302660. IPI00845460.
RefSeq	NP_001138624.1. NM_001145152.1. NP_689628.2. NM_152415.2.
UniGene	Hs.343873.
3D structure databases
ProteinModelPortal	Q8NEZ2.
SMR	Q8NEZ2. Positions 60-124, 321-379.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8NEZ2. 2 interactions.
MINT	MINT-2811404.
STRING	9606.ENSP00000318629.
PTM databases
PhosphoSite	Q8NEZ2.
Polymorphism databases
DMDM	74715446.
Proteomic databases
PaxDb	Q8NEZ2.
PRIDE	Q8NEZ2.
Protocols and materials databases
DNASU	137492.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324815; ENSP00000318173; ENSG00000155975. ENST00000324849; ENSP00000318629; ENSG00000155975. ENST00000425020; ENSP00000412824; ENSG00000155975. ENST00000521829; ENSP00000429680; ENSG00000155975.
GeneID	137492.
KEGG	hsa:137492.
UCSC	uc003wxj.3. human. uc003wxk.3. human.
Organism-specific databases
CTD	137492.
GeneCards	GC08P017149.
HGNC	HGNC:24928. VPS37A.
HPA	HPA024705. HPA024781.
MIM	609927. gene. 614898. phenotype.
neXtProt	NX_Q8NEZ2.
Orphanet	319199. Autosomal recessive spastic paraplegia type 53.
PharmGKB	PA142670615.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG243233.
HOGENOM	HOG000008031.
HOVERGEN	HBG054793.
InParanoid	Q8NEZ2.
KO	K12185.
OMA	PPYASQG.
OrthoDB	EOG4RBQK8.
PhylomeDB	Q8NEZ2.
Enzyme and pathway databases
Reactome	REACT_11123. Membrane Trafficking. REACT_116125. Disease.
Gene expression databases
ArrayExpress	Q8NEZ2.
Bgee	Q8NEZ2.
CleanEx	HS_VPS37A.
Genevestigator	Q8NEZ2.
Family and domain databases
Gene3D	3.10.110.10. 1 hit.
InterPro	IPR009851. Mod_r. IPR016135. UBQ-conjugating_enzyme/RWD. [Graphical view]
Pfam	PF07200. Mod_r. 1 hit. [Graphical view]
SUPFAM	SSF54495. UBQ-conjugat/RWD-like. 1 hit.
PROSITE	PS51314. VPS37_C. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	VPS37A. human.
GenomeRNAi	137492.
NextBio	83653.
SOURCE	Search...

Entry information

Entry name

VP37A_HUMAN

Accession

Primary (citable) accession number: Q8NEZ2
Secondary accession number(s): Q336D5 , Q6NW27, Q8N3D7, Q8TBL7, Q96DL9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 15, 2007
Last sequence update:	October 1, 2002
Last modified:	May 29, 2013
This is version 86 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.