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Database: UniProt
Entry: RIN2_HUMAN
LinkDB: RIN2_HUMAN
Original site: RIN2_HUMAN 
ID   RIN2_HUMAN              Reviewed;         895 AA.
AC   Q8WYP3; Q00425; Q5TFT8; Q9BQL3; Q9H071;
DT   01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   08-MAY-2019, entry version 145.
DE   RecName: Full=Ras and Rab interactor 2;
DE   AltName: Full=Ras association domain family 4;
DE   AltName: Full=Ras inhibitor JC265;
DE   AltName: Full=Ras interaction/interference protein 2;
GN   Name=RIN2; Synonyms=RASSF4;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION,
RP   AND INTERACTION WITH RAB5B.
RC   TISSUE=Leukocyte;
RX   PubMed=11733506; DOI=10.1074/jbc.M106276200;
RA   Saito K., Murai J., Kajiho H., Kontani K., Kurosu H., Katada T.;
RT   "A novel binding protein composed of homophilic tetramer exhibits
RT   unique properties for the small GTPase Rab5.";
RL   J. Biol. Chem. 277:3412-3418(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA   Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA   Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA   Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA   Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA   Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA   Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA   Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA   Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA   Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA   Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA   Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA   Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-852 (ISOFORM 2), AND
RP   VARIANT THR-197.
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 29-895 (ISOFORMS 1/2).
RC   TISSUE=Uterus;
RX   PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA   Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA   Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA   Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA   Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA   Wambutt R., Korn B., Klein M., Poustka A.;
RT   "Towards a catalog of human genes and proteins: sequencing and
RT   analysis of 500 novel complete protein coding human cDNAs.";
RL   Genome Res. 11:422-435(2001).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 425-895 (ISOFORMS 1/2), AND INTERACTION
RP   WITH RAS.
RC   TISSUE=Glial cell;
RX   PubMed=1849280; DOI=10.1073/pnas.88.7.2913;
RA   Colicelli J., Nicolette C., Birchmeier C., Rodgers L., Riggs M.,
RA   Wigler M.;
RT   "Expression of three mammalian cDNAs that interfere with RAS function
RT   in Saccharomyces cerevisiae.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:2913-2917(1991).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-509, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=18318008; DOI=10.1002/pmic.200700884;
RA   Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA   Zou H., Gu J.;
RT   "Large-scale phosphoproteome analysis of human liver tissue by
RT   enrichment and fractionation of phosphopeptides with strong anion
RT   exchange chromatography.";
RL   Proteomics 8:1346-1361(2008).
RN   [7]
RP   INVOLVEMENT IN MACS SYNDROME.
RX   PubMed=19631308; DOI=10.1016/j.ajhg.2009.07.001;
RA   Basel-Vanagaite L., Sarig O., Hershkovitz D., Fuchs-Telem D.,
RA   Rapaport D., Gat A., Isman G., Shirazi I., Shohat M., Enk C.D.,
RA   Birk E., Kohlhase J., Matysiak-Scholze U., Maya I., Knopf C.,
RA   Peffekoven A., Hennies H.-C., Bergman R., Horowitz M.,
RA   Ishida-Yamamoto A., Sprecher E.;
RT   "RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and
RT   scoliosis: MACS syndrome.";
RL   Am. J. Hum. Genet. 85:254-263(2009).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: Ras effector protein. May function as an upstream
CC       activator and/or downstream effector for RAB5B in endocytic
CC       pathway. May function as a guanine nucleotide exchange (GEF) of
CC       RAB5B, required for activating the RAB5 proteins by exchanging
CC       bound GDP for free GTP. {ECO:0000269|PubMed:11733506}.
CC   -!- SUBUNIT: Homotetramer; probably composed of anti-parallel linkage
CC       of two parallel dimers. Interacts with Ras. Interacts with RAB5B,
CC       with a much higher affinity for GTP-bound activated RAB5B. Does
CC       not interact with other members of the Rab family.
CC       {ECO:0000269|PubMed:11733506, ECO:0000269|PubMed:1849280}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8WYP3-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8WYP3-2; Sequence=VSP_015145;
CC         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Widely expressed. Expressed in heart, kidney,
CC       lung placenta. Expressed at low level in skeletal muscle, spleen
CC       and peripheral blood. {ECO:0000269|PubMed:11733506}.
CC   -!- DISEASE: MACS syndrome (MACS) [MIM:613075]: A complex disorder of
CC       elastic tissue characterized by sagging skin and occasionally by
CC       life-threatening visceral complications.
CC       {ECO:0000269|PubMed:19631308}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the RIN (Ras interaction/interference)
CC       family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAB66858.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
DR   EMBL; AB060339; BAB84317.1; -; mRNA.
DR   EMBL; AL049538; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL132821; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AK094884; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AL136924; CAB66858.1; ALT_INIT; mRNA.
DR   EMBL; M37190; AAA36553.1; -; mRNA.
DR   CCDS; CCDS56182.1; -. [Q8WYP3-2]
DR   PIR; B38637; B38637.
DR   RefSeq; NP_001229510.1; NM_001242581.1. [Q8WYP3-2]
DR   RefSeq; NP_061866.1; NM_018993.3. [Q8WYP3-1]
DR   RefSeq; XP_005260788.1; XM_005260731.2. [Q8WYP3-1]
DR   RefSeq; XP_006723637.1; XM_006723574.3. [Q8WYP3-1]
DR   RefSeq; XP_006723638.1; XM_006723575.3. [Q8WYP3-1]
DR   RefSeq; XP_006723640.1; XM_006723577.2. [Q8WYP3-1]
DR   RefSeq; XP_011527559.1; XM_011529257.1. [Q8WYP3-1]
DR   RefSeq; XP_011527560.1; XM_011529258.2. [Q8WYP3-1]
DR   RefSeq; XP_016883376.1; XM_017027887.1. [Q8WYP3-2]
DR   RefSeq; XP_016883377.1; XM_017027888.1. [Q8WYP3-2]
DR   RefSeq; XP_016883379.1; XM_017027890.1. [Q8WYP3-1]
DR   BioGrid; 119960; 12.
DR   IntAct; Q8WYP3; 3.
DR   MINT; Q8WYP3; -.
DR   STRING; 9606.ENSP00000255006; -.
DR   iPTMnet; Q8WYP3; -.
DR   PhosphoSitePlus; Q8WYP3; -.
DR   BioMuta; RIN2; -.
DR   DMDM; 28201876; -.
DR   EPD; Q8WYP3; -.
DR   jPOST; Q8WYP3; -.
DR   MaxQB; Q8WYP3; -.
DR   PaxDb; Q8WYP3; -.
DR   PeptideAtlas; Q8WYP3; -.
DR   PRIDE; Q8WYP3; -.
DR   ProteomicsDB; 75179; -.
DR   ProteomicsDB; 75180; -. [Q8WYP3-2]
DR   Ensembl; ENST00000255006; ENSP00000255006; ENSG00000132669. [Q8WYP3-2]
DR   Ensembl; ENST00000648440; ENSP00000498085; ENSG00000132669. [Q8WYP3-1]
DR   GeneID; 54453; -.
DR   KEGG; hsa:54453; -.
DR   UCSC; uc002wro.3; human. [Q8WYP3-1]
DR   CTD; 54453; -.
DR   DisGeNET; 54453; -.
DR   GeneCards; RIN2; -.
DR   HGNC; HGNC:18750; RIN2.
DR   HPA; HPA034641; -.
DR   MalaCards; RIN2; -.
DR   MIM; 610222; gene.
DR   MIM; 613075; phenotype.
DR   neXtProt; NX_Q8WYP3; -.
DR   OpenTargets; ENSG00000132669; -.
DR   Orphanet; 217335; RIN2 syndrome.
DR   PharmGKB; PA38672; -.
DR   eggNOG; KOG2320; Eukaryota.
DR   eggNOG; ENOG410ZZW5; LUCA.
DR   GeneTree; ENSGT00940000154866; -.
DR   InParanoid; Q8WYP3; -.
DR   OMA; ESRPPCH; -.
DR   OrthoDB; 1311692at2759; -.
DR   PhylomeDB; Q8WYP3; -.
DR   TreeFam; TF331067; -.
DR   Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR   ChiTaRS; RIN2; human.
DR   GenomeRNAi; 54453; -.
DR   PRO; PR:Q8WYP3; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   Bgee; ENSG00000132669; Expressed in 241 organ(s), highest expression level in tendon.
DR   ExpressionAtlas; Q8WYP3; baseline and differential.
DR   Genevisible; Q8WYP3; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR   GO; GO:0030695; F:GTPase regulator activity; NAS:UniProtKB.
DR   GO; GO:0017112; F:Rab guanyl-nucleotide exchange factor activity; NAS:UniProtKB.
DR   GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR   GO; GO:0007264; P:small GTPase mediated signal transduction; NAS:UniProtKB.
DR   CDD; cd10394; SH2_RIN2; 1.
DR   Gene3D; 1.20.1050.80; -; 1.
DR   Gene3D; 3.30.505.10; -; 1.
DR   InterPro; IPR000159; RA_dom.
DR   InterPro; IPR035868; RIN2_SH2.
DR   InterPro; IPR000980; SH2.
DR   InterPro; IPR036860; SH2_dom_sf.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   InterPro; IPR003123; VPS9.
DR   InterPro; IPR037191; VPS9_dom_sf.
DR   Pfam; PF00788; RA; 1.
DR   Pfam; PF02204; VPS9; 1.
DR   SMART; SM00314; RA; 1.
DR   SMART; SM00167; VPS9; 1.
DR   SUPFAM; SSF109993; SSF109993; 1.
DR   SUPFAM; SSF54236; SSF54236; 1.
DR   SUPFAM; SSF55550; SSF55550; 1.
DR   PROSITE; PS50200; RA; 1.
DR   PROSITE; PS50001; SH2; 1.
DR   PROSITE; PS51205; VPS9; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Complete proteome; Cytoplasm; Endocytosis;
KW   GTPase activation; Phosphoprotein; Polymorphism; Reference proteome;
KW   SH2 domain.
FT   CHAIN         1    895       Ras and Rab interactor 2.
FT                                /FTId=PRO_0000191320.
FT   DOMAIN       97    190       SH2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00191}.
FT   DOMAIN      618    757       VPS9. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00550}.
FT   DOMAIN      787    878       Ras-associating. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00166}.
FT   COMPBIAS    307    314       Poly-Pro.
FT   MOD_RES     366    366       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q9D684}.
FT   MOD_RES     501    501       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q9D684}.
FT   MOD_RES     509    509       Phosphothreonine.
FT                                {ECO:0000244|PubMed:18318008}.
FT   VAR_SEQ       1      1       M -> MLDSFSQESTLPFREARKRTSFQPVQVWRNFTASQT
FT                                TESPACSGASLGEM (in isoform 2).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_015145.
FT   VARIANT     197    197       S -> T (in dbSNP:rs3803981).
FT                                {ECO:0000269|PubMed:14702039}.
FT                                /FTId=VAR_024694.
FT   VARIANT     643    643       A -> T (in dbSNP:rs199603).
FT                                /FTId=VAR_052945.
FT   CONFLICT    192    192       I -> V (in Ref. 3; AK094884).
FT                                {ECO:0000305}.
SQ   SEQUENCE   895 AA;  100163 MW;  0DECDBF8D2629EE4 CRC64;
     MTAWTMGARG LDKRGSFFKL IDTIASEIGE LKQEMVRTDV NLENGLEPAE THSMVRHKDG
     GYSEEEDVKT CARDSGYDSL SNRLSILDRL LHTHPIWLQL SLSEEEAAEV LQAQPPGIFL
     VHKSTKMQKK VLSLRLPCEF GAPLKEFAIK ESTYTFSLEG SGISFADLFR LIAFYCISRD
     VLPFTLKLPY AISTAKSEAQ LEELAQMGLN FWSSPADSKP PNLPPPHRPL SSDGVCPASL
     RQLCLINGVH SIKTRTPSEL ECSQTNGALC FINPLFLKVH SQDLSGGLKR PSTRTPNANG
     TERTRSPPPR PPPPAINSLH TSPRLARTET QTSMPETVNH NKHGNVALPG TKPTPIPPPR
     LKKQASFLEA EGGAKTLSGG RPGAGPELEL GTAGSPGGAP PEAAPGDCTR APPPSSESRP
     PCHGGRQRLS DMSISTSSSD SLEFDRSMPL FGYEADTNSS LEDYEGESDQ ETMAPPIKSK
     KKRSSSFVLP KLVKSQLQKV SGVFSSFMTP EKRMVRRIAE LSRDKCTYFG CLVQDYVSFL
     QENKECHVSS TDMLQTIRQF MTQVKNYLSQ SSELDPPIES LIPEDQIDVV LEKAMHKCIL
     KPLKGHVEAM LKDFHMADGS WKQLKENLQL VRQRNPQELG VFAPTPDFVD VEKIKVKFMT
     MQKMYSPEKK VMLLLRVCKL IYTVMENNSG RMYGADDFLP VLTYVIAQCD MLELDTEIEY
     MMELLDPSLL HGEGGYYLTS AYGALSLIKN FQEEQAARLL SSETRDTLRQ WHKRRTTNRT
     IPSVDDFQNY LRVAFQEVNS GCTGKTLLVR PYITTEDVCQ ICAEKFKVGD PEEYSLFLFV
     DETWQQLAED TYPQKIKAEL HSRPQPHIFH FVYKRIKNDP YGIIFQNGEE DLTTS
//
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