Q13596 (SNX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sorting nexin-1

Gene names

Name:

SNX1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	522 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be involved in several stages of intracellular trafficking. Plays a role in targeting ligand-activated EGFR to the lysosomes for degradation after endocytosis from the cell surface and release from the Golgi. Component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Ref.8 Ref.10 Ref.11
Subunit structure	Homodimer. Self-assembles into a complex of approximately 300 kDa By similarity. Interacts with HGS By similarity. Component of the retromer complex composed of VPS26 (VPS26A or VPS26B), VPS29, VPS35, SNX1 and SNX2. Interacts with SNX6. Ref.2 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13
Subcellular location	Endosome membrane; Peripheral membrane protein; Cytoplasmic side. Golgi apparatus › trans-Golgi network membrane; Peripheral membrane protein; Cytoplasmic side Potential. Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Note: Enriched on tubular elements of the early endosome membrane. Binds preferentially to highly curved membranes enriched in phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Ref.8 Ref.9 Ref.10 Ref.11 Ref.17
Miscellaneous	Binds phosphatidylinositol 3-phosphate (PtdIns-3P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2) in liposome-based assays. Can bind PtdIns(3,4,5)P3 in protein:lipid overlay assays, but not in liposome-based assays.
Sequence similarities	Belongs to the sorting nexin family. Contains 1 BAR domain. Contains 1 PX (phox homology) domain.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Endosome Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Lipid-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell communication Inferred from electronic annotation. Source: InterPro early endosome to Golgi transport Inferred from mutant phenotype Ref.10. Source: UniProtKB endocytosis Traceable author statement. Source: ProtInc intracellular protein transport Inferred from mutant phenotype Ref.10. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell early endosome membrane Inferred from direct assay Ref.10. Source: UniProtKB
Molecular function	phosphatidylinositol binding Inferred from direct assay Ref.10. Source: UniProtKB protein binding Inferred from physical interaction Ref.13. Source: UniProtKB protein transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13596-1)

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 1A (identifier: Q13596-2)

The sequence of this isoform differs from the canonical sequence as follows:
     91-155: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 522

522

Sorting nexin-1

PRO_0000213835

Regions

Domain

143 – 272

130

PX

Domain

302 – 522

221

BAR

Sites

Binding site

186

1

Phosphatidylinositol 3-phosphate By similarity

Binding site

188

1

Phosphatidylinositol 3-phosphate; via amide nitrogen and carbonyl oxygen By similarity

Binding site

214

1

Phosphatidylinositol 3-phosphate By similarity

Binding site

238

1

Phosphatidylinositol 3-phosphate By similarity

Amino acid modifications

Modified residue

32

1

Phosphoserine Ref.12

Modified residue

39

1

Phosphoserine Ref.12

Modified residue

41

1

Phosphothreonine Ref.12

Modified residue

188

1

Phosphoserine Ref.12 Ref.14

Modified residue

237

1

N6-acetyllysine Ref.15

Natural variations

Alternative sequence

91 – 155

65

Missing in isoform 1A.

VSP_006189

Natural variant

115

1

S → Y.
Corresponds to variant rs1049501 [ dbSNP | Ensembl ].

VAR_052477

Natural variant

466

1

D → N.
Corresponds to variant rs1802376 [ dbSNP | Ensembl ].

VAR_034507

Experimental info

Mutagenesis

214

1

K → A: Abolishes phosphatidylinositol phosphate binding. Abolishes endosomal location. Ref.8 Ref.10

Mutagenesis

429 – 431

3

KKR → EEE: Loss of endosomal location. Ref.10

Sequence conflict

117

1

P → S in AAC17182. Ref.2

Sequence conflict

211

1

P → S in AAC17182. Ref.2

Sequence conflict

211

1

P → S in AAC17183. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

522

Helix Strand Turn

Details...

Beta strand

173 – 176

4

Helix

187 – 199

13

Beta strand

202 – 205

4

Beta strand

210 – 213

4

Beta strand

216 – 221

6

Helix

234 – 251

18

Helix

253 – 256

4

Helix

259 – 262

4

Turn

263 – 266

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 16, 2001. Version 3. Checksum: 6AC8AA0A589513E3	FASTA	522	59,070
	10 20 30 40 50 60 MASGGGGCSA SERLPPPFPG LEPESEGAAG GSEPEAGDSD TEGEDIFTGA AVVSKHQSPK 70 80 90 100 110 120 ITTSLLPINN GSKENGIHEE QDQEPQDLFA DATVELSLDS TQNNQKKVLA KTLISLPPQE 130 140 150 160 170 180 ATNSSKPQPT YEELEEEEQE DQFDLTVGIT DPEKIGDGMN AYVAYKVTTQ TSLPLFRSKQ 190 200 210 220 230 240 FAVKRRFSDF LGLYEKLSEK HSQNGFIVPP PPEKSLIGMT KVKVGKEDSS SAEFLEKRRA 250 260 270 280 290 300 ALERYLQRIV NHPTMLQDPD VREFLEKEEL PRAVGTQTLS GAGLLKMFNK ATDAVSKMTI 310 320 330 340 350 360 KMNESDIWFE EKLQEVECEE QRLRKLHAVV ETLVNHRKEL ALNTAQFAKS LAMLGSSEDN 370 380 390 400 410 420 TALSRALSQL AEVEEKIEQL HQEQANNDFF LLAELLSDYI RLLAIVRAAF DQRMKTWQRW 430 440 450 460 470 480 QDAQATLQKK REAEARLLWA NKPDKLQQAK DEILEWESRV TQYERDFERI STVVRKEVIR 490 500 510 520 FEKEKSKDFK NHVIKYLETL LYSQQQLAKY WEAFLPEAKA IS
	Isoform 1A [UniParc]. Checksum: 3F844B9E84C258C2	FASTA	457	51,813
	10 20 30 40 50 60 MASGGGGCSA SERLPPPFPG LEPESEGAAG GSEPEAGDSD TEGEDIFTGA AVVSKHQSPK 70 80 90 100 110 120 ITTSLLPINN GSKENGIHEE QDQEPQDLFA GDGMNAYVAY KVTTQTSLPL FRSKQFAVKR 130 140 150 160 170 180 RFSDFLGLYE KLSEKHSQNG FIVPPPPEKS LIGMTKVKVG KEDSSSAEFL EKRRAALERY 190 200 210 220 230 240 LQRIVNHPTM LQDPDVREFL EKEELPRAVG TQTLSGAGLL KMFNKATDAV SKMTIKMNES 250 260 270 280 290 300 DIWFEEKLQE VECEEQRLRK LHAVVETLVN HRKELALNTA QFAKSLAMLG SSEDNTALSR 310 320 330 340 350 360 ALSQLAEVEE KIEQLHQEQA NNDFFLLAEL LSDYIRLLAI VRAAFDQRMK TWQRWQDAQA 370 380 390 400 410 420 TLQKKREAEA RLLWANKPDK LQQAKDEILE WESRVTQYER DFERISTVVR KEVIRFEKEK 430 440 450 SKDFKNHVIK YLETLLYSQQ QLAKYWEAFL PEAKAIS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Enhanced degradation of EGF receptors by a sorting nexin, SNX1." Kurten R.C., Cadena D.L., Gill G.N. Science 272:1008-1010(1996) [PubMed: 8638121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Identification of a family of sorting nexin molecules and characterization of their association with receptors." Haft C.R., de la Luz Sierra M., Barr V.A., Haft D.H., Taylor S.I. Mol. Cell. Biol. 18:7278-7287(1998) [PubMed: 9819414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, INTERACTION WITH VPS26A; VPS29; VPS35 AND SNX2.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[5]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed: 16572171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle.
[8]	"The phox homology (PX) domain-dependent, 3-phosphoinositide-mediated association of sorting nexin-1 with an early sorting endosomal compartment is required for its ability to regulate epidermal growth factor receptor degradation." Cozier G.E., Carlton J., McGregor A.H., Gleeson P.A., Teasdale R.D., Mellor H., Cullen P.J. J. Biol. Chem. 277:48730-48736(2002) [PubMed: 12198132] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-214, INTERACTION WITH PHOSPHATIDYLINOSITIDES.
[9]	"Endosomal localization and function of sorting nexin 1." Zhong Q., Lazar C.S., Tronchere H., Sato T., Meerloo T., Yeo M., Songyang Z., Emr S.D., Gill G.N. Proc. Natl. Acad. Sci. U.S.A. 99:6767-6772(2002) [PubMed: 11997453] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH SNX2.
[10]	"Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence sensing of high- curvature membranes and 3-phosphoinositides." Carlton J., Bujny M., Peter B.J., Oorschot V.M., Rutherford A., Mellor H., Klumperman J., McMahon H.T., Cullen P.J. Curr. Biol. 14:1791-1800(2004) [PubMed: 15498486] [Abstract] Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-214 AND 429-LYS--ARG-431.
[11]	"Interchangeable but essential functions of SNX1 and SNX2 in the association of retromer with endosomes and the trafficking of mannose 6-phosphate receptors." Rojas R., Kametaka S., Haft C.R., Bonifacino J.S. Mol. Cell. Biol. 27:1112-1124(2007) [PubMed: 17101778] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT.
[12]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; SER-39; THR-41 AND SER-188, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"The retromer component SNX6 interacts with dynactin p150(Glued) and mediates endosome-to-TGN transport." Hong Z., Yang Y., Zhang C., Niu Y., Li K., Zhao X., Liu J.J. Cell Res. 19:1334-1349(2009) [PubMed: 19935774] [Abstract] Cited for: INTERACTION WITH SNX6.
[14]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-237, MASS SPECTROMETRY.
[16]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"Determinants of the endosomal localization of sorting nexin 1." Zhong Q., Watson M.J., Lazar C.S., Hounslow A.M., Waltho J.P., Gill G.N. Mol. Biol. Cell 16:2049-2057(2005) [PubMed: 15673616] [Abstract] Cited for: STRUCTURE BY NMR OF 142-269, SUBCELLULAR LOCATION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U53225 mRNA. Translation: AAA98672.1.
AF065483 mRNA. Translation: AAC17182.1.
AF065484 mRNA. Translation: AAC17183.1.
BT006983 mRNA. Translation: AAP35629.1.
AK291752 mRNA. Translation: BAF84441.1.
AC021541 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77663.1.
CH471082 Genomic DNA. Translation: EAW77665.1.
BC000357 mRNA. Translation: AAH00357.1.

IPI

IPI00183530.
IPI00220527.

PIR

G02522.

RefSeq

NP_003090.2. NM_003099.4.
NP_683758.1. NM_148955.3.

UniGene

Hs.188634.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I4K	NMR	-	A	142-269	[»]

ProteinModelPortal

Q13596.

SMR

Q13596. Positions 142-269.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-398N.

IntAct

Q13596. 4 interactions.

STRING

Q13596.

PTM databases

PhosphoSite

Q13596.

Polymorphism databases

DMDM

17380569.

Proteomic databases

PRIDE

Q13596.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380285; ENSP00000369638; ENSG00000028528.

GeneID

6642.

KEGG

hsa:6642.

UCSC

uc002amv.1. human.
uc002amx.1. human.

Organism-specific databases

CTD

6642.

GeneCards

GC15P064388.

H-InvDB

HIX0012335.

HGNC

HGNC:11172. SNX1.

MIM

601272. gene.

neXtProt

NX_Q13596.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG10321.

HOVERGEN

HBG000618.

InParanoid

Q13596.

OMA

INNGSKE.

OrthoDB

EOG418BNH.

PhylomeDB

Q13596.

Gene expression databases

ArrayExpress

Q13596.

Bgee

Q13596.

CleanEx

HS_SNX1.

Genevestigator

Q13596.

GermOnline

ENSG00000028528. Homo sapiens.

Family and domain databases

InterPro

IPR001683. Phox.
IPR005329. Sorting_nexin_N.
IPR015404. Vps5_C.
[Graphical view]

Gene3D

G3DSA:3.30.1520.10. PX. 1 hit.

Pfam

PF00787. PX. 1 hit.
PF03700. Sorting_nexin. 1 hit.
PF09325. Vps5. 1 hit.
[Graphical view]

SMART

SM00312. PX. 1 hit.
[Graphical view]

SUPFAM

SSF64268. PX. 1 hit.

PROSITE

PS51021. BAR. False negative.
PS50195. PX. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

25881.

SOURCE

Search...

Entry information

Entry name

SNX1_HUMAN

Accession

Primary (citable) accession number: Q13596
Secondary accession number(s): A6NM19 , A8K6T7, O60750, O60751

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 16, 2001
Last modified:	January 25, 2012
This is version 107 of the entry and version 3 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.