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Q96QK1 (VPS35_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length796 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 796796Vacuolar protein sorting-associated protein 35
PRO_0000065896

Amino acid modifications

Modified residue71Phosphoserine Ref.12
Modified residue7911Phosphotyrosine By similarity

Natural variations

Natural variant511G → S. Ref.16
VAR_066653
Natural variant571M → I. Ref.16
VAR_066654
Natural variant821T → R. Ref.16
VAR_066655
Natural variant2411I → M Found in a patient with Parkinson disease. Ref.16
VAR_066656
Natural variant3161P → S Found in a patient with Parkinson disease. Ref.15
VAR_066657
Natural variant5241R → W Found in a patient with Parkinson disease. Ref.16
VAR_066658
Natural variant6021V → D.
Corresponds to variant rs34687100 [ dbSNP | Ensembl ].
VAR_054046
Natural variant6201D → N in PARK17. Ref.15 Ref.16 Ref.17
VAR_066659
Natural variant7371A → V. Ref.15
VAR_066660
Natural variant7741L → M. Ref.16
VAR_066661

Experimental info

Sequence conflict421A → S in CAB66822. Ref.6
Sequence conflict1601I → T in BAB14626. Ref.5
Sequence conflict1681T → P in AAF89953. Ref.3
Sequence conflict4531S → F in AAH10362. Ref.7
Sequence conflict5261R → G in BAA91790. Ref.5
Sequence conflict6941K → E in BAA91790. Ref.5
Sequence conflict7961L → H in BAA91137. Ref.5

Secondary structure

.................................... 796
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q96QK1 [UniParc].

Last modified November 25, 2002. Version 2.
Checksum: 28D2DD1C6B920A0A

FASTA79691,707
        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 

« Hide

References

« Hide '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. 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].
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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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. expand/collapse author list , 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. expand/collapse author list , 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.
PIRJC7516.
RefSeqNP_060676.2. NM_018206.4.
UniGeneHs.454528.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2R17X-ray2.80C/D483-780[»]
ProteinModelPortalQ96QK1.
SMRQ96QK1. Positions 483-780.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120855. 61 interactions.
DIPDIP-29076N.
IntActQ96QK1. 18 interactions.
MINTMINT-5001902.

Chemistry

ChEMBLCHEMBL2216744.

PTM databases

PhosphoSiteQ96QK1.

Polymorphism databases

DMDM25453321.

Proteomic databases

PaxDbQ96QK1.
PeptideAtlasQ96QK1.
PRIDEQ96QK1.

Protocols and materials databases

DNASU55737.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000299138; ENSP00000299138; ENSG00000069329.
GeneID55737.
KEGGhsa:55737.
UCSCuc002eed.3. human.

Organism-specific databases

CTD55737.
GeneCardsGC16M046691.
HGNCHGNC:13487. VPS35.
HPAHPA040802.
MIM601501. gene.
614203. phenotype.
neXtProtNX_Q96QK1.
Orphanet2828. Young adult-onset Parkinsonism.
PharmGKBPA37783.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG252873.
HOVERGENHBG054277.
InParanoidQ96QK1.
OMAVNCRDSL.
OrthoDBEOG7TMZR5.
PhylomeDBQ96QK1.
TreeFamTF105659.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeQ96QK1.
GenevestigatorQ96QK1.

Family and domain databases

InterProIPR016024. ARM-type_fold.
IPR005378. Vps35.
[Graphical view]
PANTHERPTHR11099. PTHR11099. 1 hit.
PfamPF03635. Vps35. 1 hit.
[Graphical view]
PIRSFPIRSF009375. Retromer_Vps35. 1 hit.
SUPFAMSSF48371. SSF48371. 3 hits.
ProtoNetSearch...

Other

ChiTaRSVPS35. human.
EvolutionaryTraceQ96QK1.
GeneWikiVPS35.
GenomeRNAi55737.
NextBio60680.
PROQ96QK1.
SOURCESearch...

Entry information

Entry nameVPS35_HUMAN
AccessionPrimary (citable) accession number: Q96QK1
Secondary accession number(s): Q561W2 expand/collapse secondary AC list , 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: April 16, 2014
This is version 126 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 16

Human chromosome 16: entries, gene names and cross-references to MIM