Reviewed, UniProtKB/Swiss-Prot Q8WYP3 (RIN2_HUMAN)

Names and origin

Protein names

Recommended name:
    Ras and Rab interactor 2
Alternative name(s):
    Ras interaction/interference protein 2
    Ras inhibitor JC265
    Ras association domain family 4

Gene names

Name:	RIN2
Synonyms:	RASSF4

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	895 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Ras effector protein. May function as an upstream activator and/or downstream effector for RAB5B in endocytic pathway. May function as a guanine nucleotide exchange (GEF) of RAB5B, required for activating the RAB5 proteins by exchanging bound GDP for free GTP. Ref.1
Subunit structure	Homotetramer; probably composed of anti-parallel linkage of two parallel dimers. Interacts with Ras. Interacts with RAB5B, with a much higher affinity for GTP-bound activated RAB5B. Does not interact with other members of the Rab family. Ref.1 Ref.5
Subcellular location	Cytoplasm Probable.
Tissue specificity	Widely expressed. Expressed in heart, kidney, lung placenta. Expressed at low level in skeletal muscle, spleen and peripheral blood. Ref.1
Sequence similarities	Belongs to the RIN (Ras interaction/interference) family. Contains 1 Ras-associating domain. Contains 1 SH2 domain. Contains 1 VPS9 domain.

Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH2 domain
Molecular function	GTPase activation
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	endocytosis Inferred from electronic annotation. Source: UniProtKB-KW small GTPase mediated signal transduction Ref.5 Non-traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	GTPase activator activity Inferred from electronic annotation. Source: UniProtKB-KW Rab guanyl-nucleotide exchange factor activity Ref.1 Non-traceable author statement. Source: UniProtKB protein binding 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: Q8WYP3-1)

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: Q8WYP3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLDSFSQESTLPFREARKRTSFQPVQVWRNFTASQTTESPACSGASLGEM

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 895	895	Ras and Rab interactor 2		PRO_0000191320
Regions
	Domain	97 – 190	94	SH2
	Domain	618 – 757	140	VPS9
	Domain	787 – 878	92	Ras-associating
	Compositional bias	307 – 314	8	Poly-Pro
Amino acid modifications
	Modified residue	366	1	Phosphoserine By similarity
	Modified residue	501	1	Phosphoserine By similarity
	Modified residue	509	1	Phosphothreonine Ref.6
Natural variations
	Alternative sequence	1	1	M → MLDSFSQESTLPFREARKRT SFQPVQVWRNFTASQTTESP ACSGASLGEM in isoform 2.		VSP_015145
	Natural variant	197	1	S → T: dbSNP rs3803981. Ref.3		VAR_024694
	Natural variant	643	1	A → T: dbSNP rs199603.		VAR_052945
Experimental info
	Sequence conflict	192	1	I → V Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 0DECDBF8D2629EE4	FASTA	895	100,163
	10 20 30 40 50 60 MTAWTMGARG LDKRGSFFKL IDTIASEIGE LKQEMVRTDV NLENGLEPAE THSMVRHKDG 70 80 90 100 110 120 GYSEEEDVKT CARDSGYDSL SNRLSILDRL LHTHPIWLQL SLSEEEAAEV LQAQPPGIFL 130 140 150 160 170 180 VHKSTKMQKK VLSLRLPCEF GAPLKEFAIK ESTYTFSLEG SGISFADLFR LIAFYCISRD 190 200 210 220 230 240 VLPFTLKLPY AISTAKSEAQ LEELAQMGLN FWSSPADSKP PNLPPPHRPL SSDGVCPASL 250 260 270 280 290 300 RQLCLINGVH SIKTRTPSEL ECSQTNGALC FINPLFLKVH SQDLSGGLKR PSTRTPNANG 310 320 330 340 350 360 TERTRSPPPR PPPPAINSLH TSPRLARTET QTSMPETVNH NKHGNVALPG TKPTPIPPPR 370 380 390 400 410 420 LKKQASFLEA EGGAKTLSGG RPGAGPELEL GTAGSPGGAP PEAAPGDCTR APPPSSESRP 430 440 450 460 470 480 PCHGGRQRLS DMSISTSSSD SLEFDRSMPL FGYEADTNSS LEDYEGESDQ ETMAPPIKSK 490 500 510 520 530 540 KKRSSSFVLP KLVKSQLQKV SGVFSSFMTP EKRMVRRIAE LSRDKCTYFG CLVQDYVSFL 550 560 570 580 590 600 QENKECHVSS TDMLQTIRQF MTQVKNYLSQ SSELDPPIES LIPEDQIDVV LEKAMHKCIL 610 620 630 640 650 660 KPLKGHVEAM LKDFHMADGS WKQLKENLQL VRQRNPQELG VFAPTPDFVD VEKIKVKFMT 670 680 690 700 710 720 MQKMYSPEKK VMLLLRVCKL IYTVMENNSG RMYGADDFLP VLTYVIAQCD MLELDTEIEY 730 740 750 760 770 780 MMELLDPSLL HGEGGYYLTS AYGALSLIKN FQEEQAARLL SSETRDTLRQ WHKRRTTNRT 790 800 810 820 830 840 IPSVDDFQNY LRVAFQEVNS GCTGKTLLVR PYITTEDVCQ ICAEKFKVGD PEEYSLFLFV 850 860 870 880 890 DETWQQLAED TYPQKIKAEL HSRPQPHIFH FVYKRIKNDP YGIIFQNGEE DLTTS
	Isoform 2. Checksum: EB0C72971CE5BFB6	FASTA	944	105,613
	10 20 30 40 50 60 MLDSFSQEST LPFREARKRT SFQPVQVWRN FTASQTTESP ACSGASLGEM TAWTMGARGL 70 80 90 100 110 120 DKRGSFFKLI DTIASEIGEL KQEMVRTDVN LENGLEPAET HSMVRHKDGG YSEEEDVKTC 130 140 150 160 170 180 ARDSGYDSLS NRLSILDRLL HTHPIWLQLS LSEEEAAEVL QAQPPGIFLV HKSTKMQKKV 190 200 210 220 230 240 LSLRLPCEFG APLKEFAIKE STYTFSLEGS GISFADLFRL IAFYCISRDV LPFTLKLPYA 250 260 270 280 290 300 ISTAKSEAQL EELAQMGLNF WSSPADSKPP NLPPPHRPLS SDGVCPASLR QLCLINGVHS 310 320 330 340 350 360 IKTRTPSELE CSQTNGALCF INPLFLKVHS QDLSGGLKRP STRTPNANGT ERTRSPPPRP 370 380 390 400 410 420 PPPAINSLHT SPRLARTETQ TSMPETVNHN KHGNVALPGT KPTPIPPPRL KKQASFLEAE 430 440 450 460 470 480 GGAKTLSGGR PGAGPELELG TAGSPGGAPP EAAPGDCTRA PPPSSESRPP CHGGRQRLSD 490 500 510 520 530 540 MSISTSSSDS LEFDRSMPLF GYEADTNSSL EDYEGESDQE TMAPPIKSKK KRSSSFVLPK 550 560 570 580 590 600 LVKSQLQKVS GVFSSFMTPE KRMVRRIAEL SRDKCTYFGC LVQDYVSFLQ ENKECHVSST 610 620 630 640 650 660 DMLQTIRQFM TQVKNYLSQS SELDPPIESL IPEDQIDVVL EKAMHKCILK PLKGHVEAML 670 680 690 700 710 720 KDFHMADGSW KQLKENLQLV RQRNPQELGV FAPTPDFVDV EKIKVKFMTM QKMYSPEKKV 730 740 750 760 770 780 MLLLRVCKLI YTVMENNSGR MYGADDFLPV LTYVIAQCDM LELDTEIEYM MELLDPSLLH 790 800 810 820 830 840 GEGGYYLTSA YGALSLIKNF QEEQAARLLS SETRDTLRQW HKRRTTNRTI PSVDDFQNYL 850 860 870 880 890 900 RVAFQEVNSG CTGKTLLVRP YITTEDVCQI CAEKFKVGDP EEYSLFLFVD ETWQQLAEDT 910 920 930 940 YPQKIKAELH SRPQPHIFHF VYKRIKNDPY GIIFQNGEED LTTS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel binding protein composed of homophilic tetramer exhibits unique properties for the small GTPase Rab5." Saito K., Murai J., Kajiho H., Kontani K., Kurosu H., Katada T. J. Biol. Chem. 277:3412-3418(2002) [PubMed: 11733506] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION, INTERACTION WITH RAB5B. Tissue: Leukocyte.
[2]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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] OF 1-852 (ISOFORM 2), VARIANT THR-197.
[4]	"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: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 29-895 (ISOFORMS 1/2). Tissue: Uterus.
[5]	"Expression of three mammalian cDNAs that interfere with RAS function in Saccharomyces cerevisiae." Colicelli J., Nicolette C., Birchmeier C., Rodgers L., Riggs M., Wigler M. Proc. Natl. Acad. Sci. U.S.A. 88:2913-2917(1991) [PubMed: 1849280] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 425-895 (ISOFORMS 1/2), INTERACTION WITH RAS. Tissue: Glial cell.
[6]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-509, MASS SPECTROMETRY. Tissue: Liver.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB060339 mRNA. Translation: BAB84317.1. AL049538, AL132821 Genomic DNA. Translation: CAI19340.1. AL132821, AL049538 Genomic DNA. Translation: CAI23572.1. AK094884 mRNA. No translation available. AL136924 mRNA. Translation: CAB66858.1. Different initiation. M37190 mRNA. Translation: AAA36553.1.
IPI	IPI00103752. IPI00549715.
PIR	B38637.
RefSeq	NP_061866.1.
UniGene	Hs.472270
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	Q8WYP3.
Proteomic databases
PRIDE	Q8WYP3.
Genome annotation databases
Ensembl	ENSG00000132669. Homo sapiens. [Contig view]
GeneID	54453.
KEGG	hsa:54453.
Organism-specific databases
GeneCards	GC20P019818.
H-InvDB	HIX0015677.
HGNC	HGNC:18750. RIN2.
MIM	610222. gene.
PharmGKB	PA38672.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q8WYP3.
HOVERGEN	Q8WYP3.
OMA	Q8WYP3. SSTDMLQ.
Gene expression databases
ArrayExpress	Q8WYP3.
Bgee	Q8WYP3.
CleanEx	HS_RASSF4. HS_RIN2.
GermOnline	ENSG00000132669. Homo sapiens.
Family and domain databases
InterPro	IPR000159. Ras-assoc. IPR000980. SH2. IPR003123. VPS9. IPR013995. VPS9_sub. [Graphical view]
Gene3D	G3DSA:3.30.505.10. SH2. 1 hit.
Pfam	PF00788. RA. 1 hit. PF02204. VPS9. 1 hit. [Graphical view]
SMART	SM00314. RA. 1 hit. SM00252. SH2. 1 hit. SM00167. VPS9. 1 hit. [Graphical view]
PROSITE	PS50200. RA. 1 hit. PS50001. SH2. 1 hit. PS51205. VPS9. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	56681.
SOURCE	Search...

Entry information

Entry name

RIN2_HUMAN

Accession

Primary (citable) accession number: Q8WYP3
Secondary accession number(s): Q00425 , Q5TFT8, Q9BQL3, Q9H071

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 2003
Last sequence update:	March 1, 2002
Last modified:	June 16, 2009
This is version 58 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)