Q96RF0 (SNX18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sorting nexin-18

Alternative name(s):
SH3 and PX domain-containing protein 3B
Sorting nexin-associated Golgi protein 1

Gene names

Name:	SNX18
Synonyms:	SH3PXD3B, SNAG1

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	628 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 endocytosis via clathrin-coated pits, but also clathrin-independent, actin-dependent fluid-phase endocytosis. Plays a role in macropinocytosis. Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate and promotes membrane tubulation. Stimulates the GTPase activity of DNM2. Promotes DNM2 location at the plasma membrane. Ref.6 Ref.8 Ref.9
Subunit structure	Heterodimer with SNX9. Interacts with ITCH. Interacts with dynamin, SYNJ1 and WASL. Interacts with the AP-1 complex. Ref.6 Ref.7 Ref.8
Subcellular location	Endomembrane system; Peripheral membrane protein; Cytoplasmic side. Endosome membrane; Peripheral membrane protein; Cytoplasmic side. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note: Localized at sites of endocytosis at the cell membrane. Detected on newly formed macropinosomes. Partially colocalized with clathrin and dynamin at the cell membrane. Transiently recruited to clathrin-coated pits at a late stage of clathrin-coated vesicle formation. Ref.6 Ref.8 Ref.9
Domain	The PX domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate.
Sequence similarities	Belongs to the sorting nexin family. Contains 1 BAR domain. Contains 1 PX (phox homology) domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Endocytosis Protein transport Transport
Cellular component	Cell membrane Endosome Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH3 domain
Ligand	Lipid-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell communication Inferred from electronic annotation. Source: InterPro endocytosis Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of GTPase activity Inferred from direct assay Ref.8. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to internal side of plasma membrane Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	phosphatidylinositol binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96RF0-1)

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: Q96RF0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     542-628: KAWPLEQVIW...RVPLMTVLSF → ALTKVKESRR...EEALHKYDSV

Isoform 3 (identifier: Q96RF0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     592-628: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 628	628	Sorting nexin-18		PRO_0000213866
Regions
	Domain	1 – 61	61	SH3
	Domain	276 – 386	111	PX
	Domain	421 – 628	208	BAR
Sites
	Binding site	312	1	Phosphatidylinositol 4,5-bisphosphate By similarity
	Binding site	314	1	Phosphatidylinositol 4,5-bisphosphate By similarity
	Binding site	338	1	Phosphatidylinositol 4,5-bisphosphate By similarity
	Binding site	352	1	Phosphatidylinositol 4,5-bisphosphate By similarity
Natural variations
	Alternative sequence	542 – 628	87	KAWPL…TVLSF → ALTKVKESRRHVEEGKMEVQ KADGIQDRCNTISFATLAEI HHFHQIRVRDFKSQMQHFLQ QQIIFFQKVTQKLEEALHKY DSV in isoform 2.		VSP_035839
	Alternative sequence	592 – 628	37	Missing in isoform 3.		VSP_045476
	Natural variant	571	1	E → D. Ref.1 Ref.2 Corresponds to variant rs2548612 [ dbSNP | Ensembl ].		VAR_052480
	Natural variant	593	1	K → T. Ref.5 Corresponds to variant rs13162502 [ dbSNP | Ensembl ].		VAR_052481
Experimental info
	Sequence conflict	32	1	E → G in BAG65075. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: BE7B16835BA80F9C	FASTA	628	68,894
	10 20 30 40 50 60 MALRARALYD FRSENPGEIS LREHEVLSLC SEQDIEGWLE GVNSRGDRGL FPASYVQVIR 70 80 90 100 110 120 APEPGPAGDG GPGAPARYAN VPPGGFEPLP VAPPASFKPP PDAFQALLQP QQAPPPSTFQ 130 140 150 160 170 180 PPGAGFPYGG GALQPSPQQL YGGYQASQGS DDDWDDEWDD SSTVADEPGA LGSGAYPDLD 190 200 210 220 230 240 GSSSAGVGAA GRYRLSTRSD LSLGSRGGSV PPQHHPSGPK SSATVSRNLN RFSTFVKSGG 250 260 270 280 290 300 EAFVLGEASG FVKDGDKLCV VLGPYGPEWQ ENPYPFQCTI DDPTKQTKFK GMKSYISYKL 310 320 330 340 350 360 VPTHTQVPVH RRYKHFDWLY ARLAEKFPVI SVPHLPEKQA TGRFEEDFIS KRRKGLIWWM 370 380 390 400 410 420 NHMASHPVLA QCDVFQHFLT CPSSTDEKAW KQGKRKAEKD EMVGANFFLT LSTPPAAALD 430 440 450 460 470 480 LQEVESKIDG FKCFTKKMDD SALQLNHTAN EFARKQVTGF KKEYQKVGQS FRGLSQAFEL 490 500 510 520 530 540 DQQAFSVGLN QAIAFTGDAY DAIGELFAEQ PRQDLDPVMD LLALYQGHLA NFPDIIHVQK 550 560 570 580 590 600 GKAWPLEQVI WSVLCRLKGA TLTAVPLWVS ESYSTGEEAS RDVDAWVFSL ECKLDCSTGS 610 620 FLLEYLALGN EYSFSKVQRV PLMTVLSF
	Isoform 2 [UniParc]. Checksum: A348EFB754F465E9	FASTA	624	69,006
	10 20 30 40 50 60 MALRARALYD FRSENPGEIS LREHEVLSLC SEQDIEGWLE GVNSRGDRGL FPASYVQVIR 70 80 90 100 110 120 APEPGPAGDG GPGAPARYAN VPPGGFEPLP VAPPASFKPP PDAFQALLQP QQAPPPSTFQ 130 140 150 160 170 180 PPGAGFPYGG GALQPSPQQL YGGYQASQGS DDDWDDEWDD SSTVADEPGA LGSGAYPDLD 190 200 210 220 230 240 GSSSAGVGAA GRYRLSTRSD LSLGSRGGSV PPQHHPSGPK SSATVSRNLN RFSTFVKSGG 250 260 270 280 290 300 EAFVLGEASG FVKDGDKLCV VLGPYGPEWQ ENPYPFQCTI DDPTKQTKFK GMKSYISYKL 310 320 330 340 350 360 VPTHTQVPVH RRYKHFDWLY ARLAEKFPVI SVPHLPEKQA TGRFEEDFIS KRRKGLIWWM 370 380 390 400 410 420 NHMASHPVLA QCDVFQHFLT CPSSTDEKAW KQGKRKAEKD EMVGANFFLT LSTPPAAALD 430 440 450 460 470 480 LQEVESKIDG FKCFTKKMDD SALQLNHTAN EFARKQVTGF KKEYQKVGQS FRGLSQAFEL 490 500 510 520 530 540 DQQAFSVGLN QAIAFTGDAY DAIGELFAEQ PRQDLDPVMD LLALYQGHLA NFPDIIHVQK 550 560 570 580 590 600 GALTKVKESR RHVEEGKMEV QKADGIQDRC NTISFATLAE IHHFHQIRVR DFKSQMQHFL 610 620 QQQIIFFQKV TQKLEEALHK YDSV
	Isoform 3 [UniParc]. Checksum: 43574BCAEBF15EDD	FASTA	591	64,752
	10 20 30 40 50 60 MALRARALYD FRSENPGEIS LREHEVLSLC SEQDIEGWLE GVNSRGDRGL FPASYVQVIR 70 80 90 100 110 120 APEPGPAGDG GPGAPARYAN VPPGGFEPLP VAPPASFKPP PDAFQALLQP QQAPPPSTFQ 130 140 150 160 170 180 PPGAGFPYGG GALQPSPQQL YGGYQASQGS DDDWDDEWDD SSTVADEPGA LGSGAYPDLD 190 200 210 220 230 240 GSSSAGVGAA GRYRLSTRSD LSLGSRGGSV PPQHHPSGPK SSATVSRNLN RFSTFVKSGG 250 260 270 280 290 300 EAFVLGEASG FVKDGDKLCV VLGPYGPEWQ ENPYPFQCTI DDPTKQTKFK GMKSYISYKL 310 320 330 340 350 360 VPTHTQVPVH RRYKHFDWLY ARLAEKFPVI SVPHLPEKQA TGRFEEDFIS KRRKGLIWWM 370 380 390 400 410 420 NHMASHPVLA QCDVFQHFLT CPSSTDEKAW KQGKRKAEKD EMVGANFFLT LSTPPAAALD 430 440 450 460 470 480 LQEVESKIDG FKCFTKKMDD SALQLNHTAN EFARKQVTGF KKEYQKVGQS FRGLSQAFEL 490 500 510 520 530 540 DQQAFSVGLN QAIAFTGDAY DAIGELFAEQ PRQDLDPVMD LLALYQGHLA NFPDIIHVQK 550 560 570 580 590 GKAWPLEQVI WSVLCRLKGA TLTAVPLWVS ESYSTGEEAS RDVDAWVFSL E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel SH3-, Pro-rich-, and PX-domain protein of the sorting nexin family." Hong W. Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASP-571. Tissue: Cerebellum.
[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 3), VARIANT ASP-571. Tissue: Trachea.
[3]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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].
[5]	"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] (ISOFORMS 1 AND 2), VARIANT THR-593. Tissue: Placenta.
[6]	"SNX18 is an SNX9 paralog that acts as a membrane tubulator in AP-1-positive endosomal trafficking." Haberg K., Lundmark R., Carlsson S.R. J. Cell Sci. 121:1495-1505(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH THE AP-1 COMPLEX, MASS SPECTROMETRY.
[7]	"The E3 ubiquitin ligase Itch regulates sorting nexin 9 through an unconventional substrate recognition domain." Baumann C., Lindholm C.K., Rimoldi D., Levy F. FEBS J. 277:2803-2814(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ITCH.
[8]	"SNX18 shares a redundant role with SNX9 and modulates endocytic trafficking at the plasma membrane." Park J., Kim Y., Lee S., Park J.J., Park Z.Y., Sun W., Kim H., Chang S. J. Cell Sci. 123:1742-1750(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DYNAMIN; WASL AND SYNJ1, SUBUNIT.
[9]	"The SNX-PX-BAR family in macropinocytosis: the regulation of macropinosome formation by SNX-PX-BAR proteins." Wang J.T., Kerr M.C., Karunaratne S., Jeanes A., Yap A.S., Teasdale R.D. PLoS ONE 5:E13763-E13763(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF395536 mRNA. Translation: AAK82415.1. AK304195 mRNA. Translation: BAG65075.1. AC091888 Genomic DNA. No translation available. CH471123 Genomic DNA. Translation: EAW54894.1. BC060791 mRNA. Translation: AAH60791.1. BC067860 mRNA. Translation: AAH67860.1. BC117218 mRNA. Translation: AAI17219.1. BC117220 mRNA. Translation: AAI17221.1.
IPI	IPI00045219. IPI00657938.
RefSeq	NP_001096045.1. NM_001102575.1. NP_001138899.1. NM_001145427.1. NP_443102.2. NM_052870.2.
UniGene	Hs.432755. Hs.606166.
3D structure databases
ProteinModelPortal	Q96RF0.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96RF0. 4 interactions.
STRING	9606.ENSP00000317332.
PTM databases
PhosphoSite	Q96RF0.
Polymorphism databases
DMDM	215273942.
Proteomic databases
PaxDb	Q96RF0.
PRIDE	Q96RF0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000326277; ENSP00000317332; ENSG00000178996. ENST00000343017; ENSP00000342276; ENSG00000178996. ENST00000381410; ENSP00000370817; ENSG00000178996.
GeneID	112574.
KEGG	hsa:112574.
UCSC	uc003jpi.4. human. uc003jpj.4. human.
Organism-specific databases
CTD	112574.
GeneCards	GC05P053850.
H-InvDB	HIX0174367.
HGNC	HGNC:19245. SNX18.
HPA	HPA037800.
neXtProt	NX_Q96RF0.
PharmGKB	PA162404304.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5391.
HOGENOM	HOG000261633.
HOVERGEN	HBG009996.
InParanoid	Q96RF0.
OMA	EGKMEVQ.
Gene expression databases
ArrayExpress	Q96RF0.
Bgee	Q96RF0.
CleanEx	HS_SNX18.
Genevestigator	Q96RF0.
GermOnline	ENSG00000178996. Homo sapiens.
Family and domain databases
Gene3D	3.30.1520.10. 1 hit.
InterPro	IPR001683. Phox. IPR011511. SH3_2. IPR001452. SH3_domain. IPR014536. Snx9. IPR019497. Sorting_nexin_WASP-bd-dom. [Graphical view]
Pfam	PF10456. BAR_3_WASP_bdg. 1 hit. PF00787. PX. 1 hit. PF07653. SH3_2. 1 hit. [Graphical view]
PIRSF	PIRSF027744. Snx9. 1 hit.
SMART	SM00312. PX. 1 hit. SM00326. SH3. 1 hit. [Graphical view]
SUPFAM	SSF64268. PX. 1 hit. SSF50044. SH3. 1 hit.
PROSITE	PS51021. BAR. False negative. PS50195. PX. 1 hit. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	112574.
NextBio	78612.

Entry information

Entry name

SNX18_HUMAN

Accession

Primary (citable) accession number: Q96RF0
Secondary accession number(s): B4E2B3 , H7BXX3, Q05BB3, Q0VG02

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2002
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 98 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.