Q96QK1 (VPS35_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vacuolar protein sorting-associated protein 35
Short name=hVPS35

Alternative name(s):
Maternal-embryonic 3
Vesicle protein sorting 35

Gene names

Name:	VPS35
Synonyms:	MEM3
ORF Names:	TCCCTA00141

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	796 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Ref.10
Subunit structure	Component of the retromer complex composed of VPS26 (VPS26A or VPS26B), VPS29, VPS35, SNX1 and SNX2. Interacts directly with VPS26A and VPS26B. Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29, VPS35 and SFN. Interacts with GOLPH3. Ref.3 Ref.9 Ref.11
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein.
Tissue specificity	Ubiquitous. Highly expressed in heart, brain, placenta, skeletal muscle, spleen, thymus, testis, ovary, small intestine, kidney and colon.
Involvement in disease	Parkinson disease 17 (PARK17) [MIM:614203]: An autosomal dominant, adult-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.16 Ref.17
Sequence similarities	Belongs to the VPS35 family.
Sequence caution	The sequence AAG01989.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAA91137.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAB14626.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Disease	Neurodegeneration Parkinson disease Parkinsonism
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW protein transport Inferred from electronic annotation. Source: UniProtKB-KW retrograde transport, endosome to Golgi Non-traceable author statement Ref.3. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay Ref.3. Source: UniProtKB endosome Inferred from direct assay. Source: LIFEdb membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 796

796

Vacuolar protein sorting-associated protein 35

PRO_0000065896

Amino acid modifications

Modified residue

7

1

Phosphoserine Ref.12

Modified residue

791

1

Phosphotyrosine By similarity

Natural variations

Natural variant

51

1

G → S. Ref.16

VAR_066653

Natural variant

57

1

M → I. Ref.16

VAR_066654

Natural variant

82

1

T → R. Ref.16

VAR_066655

Natural variant

241

1

I → M Found in a patient with Parkinson disease. Ref.16

VAR_066656

Natural variant

316

1

P → S Found in a patient with Parkinson disease. Ref.15

VAR_066657

Natural variant

524

1

R → W Found in a patient with Parkinson disease. Ref.16

VAR_066658

Natural variant

602

1

V → D.
Corresponds to variant rs34687100 [ dbSNP | Ensembl ].

VAR_054046

Natural variant

620

1

D → N in PARK17. Ref.15 Ref.16 Ref.17

VAR_066659

Natural variant

737

1

A → V. Ref.15

VAR_066660

Natural variant

774

1

L → M. Ref.16

VAR_066661

Experimental info

Sequence conflict

42

1

A → S in CAB66822. Ref.6

Sequence conflict

160

1

I → T in BAB14626. Ref.5

Sequence conflict

168

1

T → P in AAF89953. Ref.3

Sequence conflict

453

1

S → F in AAH10362. Ref.7

Sequence conflict

526

1

R → G in BAA91790. Ref.5

Sequence conflict

694

1

K → E in BAA91790. Ref.5

Sequence conflict

796

1

L → H in BAA91137. Ref.5

Secondary structure

1

.

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796

Helix Strand Turn

Details...

Turn

484 – 487

4

Helix

488 – 498

11

Helix

503 – 518

16

Beta strand

522 – 524

3

Helix

525 – 544

20

Turn

545 – 549

5

Helix

553 – 573

21

Helix

578 – 594

17

Helix

599 – 617

19

Helix

621 – 635

15

Helix

643 – 658

16

Helix

663 – 672

10

Helix

674 – 678

5

Turn

683 – 687

5

Helix

693 – 709

17

Helix

713 – 731

19

Turn

732 – 734

3

Helix

740 – 751

12

Turn

752 – 755

4

Helix

761 – 776

16

Sequences

	Sequence		Length	Mass (Da)
	Q96QK1 [UniParc]. Last modified November 25, 2002. Version 2. Checksum: 28D2DD1C6B920A0A	FASTA	796	91,707
	10 20 30 40 50 60 MPTTQQSPQD EQEKLLDEAI QAVKVQSFQM KRCLDKNKLM DALKHASNML GELRTSMLSP 70 80 90 100 110 120 KSYYELYMAI SDELHYLEVY LTDEFAKGRK VADLYELVQY AGNIIPRLYL LITVGVVYVK 130 140 150 160 170 180 SFPQSRKDIL KDLVEMCRGV QHPLRGLFLR NYLLQCTRNI LPDEGEPTDE ETTGDISDSM 190 200 210 220 230 240 DFVLLNFAEM NKLWVRMQHQ GHSRDREKRE RERQELRILV GTNLVRLSQL EGVNVERYKQ 250 260 270 280 290 300 IVLTGILEQV VNCRDALAQE YLMECIIQVF PDEFHLQTLN PFLRACAELH QNVNVKNIII 310 320 330 340 350 360 ALIDRLALFA HREDGPGIPA DIKLFDIFSQ QVATVIQSRQ DMPSEDVVSL QVSLINLAMK 370 380 390 400 410 420 CYPDRVDYVD KVLETTVEIF NKLNLEHIAT SSAVSKELTR LLKIPVDTYN NILTVLKLKH 430 440 450 460 470 480 FHPLFEYFDY ESRKSMSCYV LSNVLDYNTE IVSQDQVDSI MNLVSTLIQD QPDQPVEDPD 490 500 510 520 530 540 PEDFADEQSL VGRFIHLLRS EDPDQQYLIL NTARKHFGAG GNQRIRFTLP PLVFAAYQLA 550 560 570 580 590 600 FRYKENSKVD DKWEKKCQKI FSFAHQTISA LIKAELAELP LRLFLQGALA AGEIGFENHE 610 620 630 640 650 660 TVAYEFMSQA FSLYEDEISD SKAQLAAITL IIGTFERMKC FSEENHEPLR TQCALAASKL 670 680 690 700 710 720 LKKPDQGRAV STCAHLFWSG RNTDKNGEEL HGGKRVMECL KKALKIANQC MDPSLQVQLF 730 740 750 760 770 780 IEILNRYIYF YEKENDAVTI QVLNQLIQKI REDLPNLESS EETEQINKHF HNTLEHLRLR 790 RESPESEGPI YEGLIL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human homologues of yeast vacuolar protein sorting 29 and 35." Edgar A.J., Polak J.M. Biochem. Biophys. Res. Commun. 277:622-630(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[2]	"Cloning and characterization of human VPS35 and mouse Vps35 and mapping of VPS35 to human chromosome 16q13-q21." Zhang P., Yu L., Gao J., Fu Q., Dai F., Zhao Y., Zheng L., Zhao S. Genomics 70:253-257(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[3]	"Human orthologs of yeast vacuolar protein sorting proteins Vps26, 29, and 35: assembly into multimeric complexes." Renfrew Haft C., de la Luz Sierra M., Bafford R., Lesniak M.A., Barr V.A., Taylor S.I. Mol. Biol. Cell 11:4105-4116(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH VPS29; VPS26A; SNX1 AND SNX2. Tissue: Colon.
[4]	"A novel gene expressed in human pheochromocytoma." Peng Y., Li Y., Tu Y., Xu S., Han Z., Fu G., Chen Z. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pheochromocytoma.
[5]	"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]. Tissue: Ileal mucosa, Placenta and Teratocarcinoma.
[6]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[7]	"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]. Tissue: Brain, Placenta and Prostate.
[8]	"Pediatric leukemia cDNA sequencing project." Zhou J., Yu W., Tang H., Mei G., Tsang Y.T.M., Bouck J., Gibbs R.A., Margolin J.F. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 469-796. Tissue: Leukemia.
[9]	"Exportin 7 defines a novel general nuclear export pathway." Mingot J.-M., Bohnsack M.T., Jaekle U., Goerlich D. EMBO J. 23:3227-3236(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH XPO7; ARHGAP1; EIF4A1; VPS26A; VPS29 AND SFN.
[10]	"The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor." Verges M., Luton F., Gruber C., Tiemann F., Reinders L.G., Huang L., Burlingame A.L., Haft C.R., Mostov K.E. Nat. Cell Biol. 6:763-769(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer." Scott K.L., Kabbarah O., Liang M.C., Ivanova E., Anagnostou V., Wu J., Dhakal S., Wu M., Chen S., Feinberg T., Huang J., Saci A., Widlund H.R., Fisher D.E., Xiao Y., Rimm D.L., Protopopov A., Wong K.K., Chin L. Nature 459:1085-1090(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GOLPH3.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"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].
[14]	"Functional architecture of the retromer cargo-recognition complex." Hierro A., Rojas A.L., Rojas R., Murthy N., Effantin G., Kajava A.V., Steven A.C., Bonifacino J.S., Hurley J.H. Nature 449:1063-1067(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 483-780 IN COMPLEX WITH VPS29, ELECTRON MICROSCOPY OF THE RETROMER COMPLEX CONTAINING VPS29; VPS35 AND VPS26.
[15]	"VPS35 mutations in Parkinson disease." Vilarino-Guell C., Wider C., Ross O.A., Dachsel J.C., Kachergus J.M., Lincoln S.J., Soto-Ortolaza A.I., Cobb S.A., Wilhoite G.J., Bacon J.A., Behrouz B., Melrose H.L., Hentati E., Puschmann A., Evans D.M., Conibear E., Wasserman W.W., Aasly J.O. , Burkhard P.R., Djaldetti R., Ghika J., Hentati F., Krygowska-Wajs A., Lynch T., Melamed E., Rajput A., Rajput A.H., Solida A., Wu R.M., Uitti R.J., Wszolek Z.K., Vingerhoets F., Farrer M.J. Am. J. Hum. Genet. 89:162-167(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PARK17 ASN-620, VARIANTS SER-316 AND VAL-737.
[16]	"A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease." Zimprich A., Benet-Pages A., Struhal W., Graf E., Eck S.H., Offman M.N., Haubenberger D., Spielberger S., Schulte E.C., Lichtner P., Rossle S.C., Klopp N., Wolf E., Seppi K., Pirker W., Reinthaler E., Harutyunyan A., Kralovics R. , Peters A., Zimprich F., Brucke T., Poewe W., Auff E., Trenkwalder C., Rost B., Ransmayr G., Winkelmann J., Meitinger T., Strom T.M. Am. J. Hum. Genet. 89:168-175(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PARK17 ASN-620, VARIANTS SER-51; ILE-57; ARG-82; MET-241; TRP-524 AND MET-774.
[17]	"Identification of VPS35 mutations replicated in French families with Parkinson disease." Lesage S., Condroyer C., Klebe S., Honore A., Tison F., Brefel-Courbon C., Durr A., Brice A. Neurology 78:1449-1450(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PARK17 ASN-620.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF191298 mRNA. Translation: AAF02778.2.
AF186382 mRNA. Translation: AAG40619.1.
AF175265 mRNA. Translation: AAF89953.1.
AF183418 mRNA. Translation: AAG09687.1.
AK001614 mRNA. Translation: BAA91790.1.
AK023650 mRNA. Translation: BAB14626.1. Different initiation.
AK000395 mRNA. Translation: BAA91137.1. Different initiation.
AL136888 mRNA. Translation: CAB66822.1.
AL512769 mRNA. Translation: CAC21686.1.
BC002414 mRNA. Translation: AAH02414.1.
BC010362 mRNA. Translation: AAH10362.1.
BC093036 mRNA. Translation: AAH93036.1.
AY007112 mRNA. Translation: AAG01989.1. Different initiation.

IPI

IPI00018931.

PIR

JC7516.

RefSeq

NP_060676.2. NM_018206.4.

UniGene

Hs.454528.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2R17	X-ray	2.80	C/D	483-780	[»]

ProteinModelPortal

Q96QK1.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29076N.

IntAct

Q96QK1. 16 interactions.

MINT

MINT-5001902.

PTM databases

PhosphoSite

Q96QK1.

Polymorphism databases

DMDM

25453321.

Proteomic databases

PaxDb

Q96QK1.

PeptideAtlas

Q96QK1.

PRIDE

Q96QK1.

Protocols and materials databases

DNASU

55737.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000299138; ENSP00000299138; ENSG00000069329.

GeneID

55737.

KEGG

hsa:55737.

UCSC

uc002eed.3. human.

Organism-specific databases

CTD

55737.

GeneCards

GC16M046691.

HGNC

HGNC:13487. VPS35.

HPA

HPA040802.

MIM

601501. gene.
614203. phenotype.

neXtProt

NX_Q96QK1.

Orphanet

2828. Young adult-onset Parkinsonism.

PharmGKB

PA37783.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG252873.

HOVERGEN

HBG054277.

InParanoid

Q96QK1.

OMA

VQLFEVF.

OrthoDB

EOG4HT8RK.

PhylomeDB

Q96QK1.

Gene expression databases

ArrayExpress

Q96QK1.

Bgee

Q96QK1.

Genevestigator

Q96QK1.

GermOnline

ENSG00000069329. Homo sapiens.

Family and domain databases

InterPro

IPR005378. VPS35.
[Graphical view]

PANTHER

PTHR11099. PTHR11099. 1 hit.

Pfam

PF03635. Vps35. 1 hit.
[Graphical view]

PIRSF

PIRSF009375. Retromer_Vps35. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

VPS35. human.

EvolutionaryTrace

Q96QK1.

GenomeRNAi

55737.

NextBio

60680.

SOURCE

Search...

Entry information

Entry name

VPS35_HUMAN

Accession

Primary (citable) accession number: Q96QK1
Secondary accession number(s): Q561W2 , Q9H016, Q9H096, Q9H4P3, Q9H8J0, Q9NRS7, Q9NVG2, Q9NX80, Q9NZK2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 25, 2002
Last sequence update:	November 25, 2002
Last modified:	May 1, 2013
This is version 117 of the entry and version 2 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.