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 03-AUG-2022, entry version 162.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION, AND
RP 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 unique
RT 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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., 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 VARIANT
RP 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 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 WITH
RP 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., Wigler M.;
RT "Expression of three mammalian cDNAs that interfere with RAS function in
RT 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 BY
RP 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 enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT 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., Rapaport D.,
RA Gat A., Isman G., Shirazi I., Shohat M., Enk C.D., Birk E., Kohlhase J.,
RA Matysiak-Scholze U., Maya I., Knopf C., Peffekoven A., Hennies H.-C.,
RA Bergman R., Horowitz M., 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., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Ras effector protein. May function as an upstream activator
CC and/or downstream effector for RAB5B in endocytic pathway. May function
CC as a guanine nucleotide exchange (GEF) of RAB5B, required for
CC activating the RAB5 proteins by exchanging bound GDP for free GTP.
CC {ECO:0000269|PubMed:11733506}.
CC -!- SUBUNIT: Homotetramer; probably composed of anti-parallel linkage of
CC two parallel dimers. Interacts with Ras. Interacts with RAB5B, with a
CC much higher affinity for GTP-bound activated RAB5B. Does not interact
CC with other members of the Rab family. {ECO:0000269|PubMed:11733506,
CC 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 -!- TISSUE SPECIFICITY: Widely expressed. Expressed in heart, kidney, lung
CC placenta. Expressed at low level in skeletal muscle, spleen and
CC 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 life-
CC threatening visceral complications. {ECO:0000269|PubMed:19631308}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the RIN (Ras interaction/interference) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB66858.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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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.
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 AlphaFoldDB; Q8WYP3; -.
DR SMR; Q8WYP3; -.
DR BioGRID; 119960; 18.
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 MassIVE; Q8WYP3; -.
DR MaxQB; Q8WYP3; -.
DR PaxDb; Q8WYP3; -.
DR PeptideAtlas; Q8WYP3; -.
DR PRIDE; Q8WYP3; -.
DR ProteomicsDB; 75179; -. [Q8WYP3-1]
DR ProteomicsDB; 75180; -. [Q8WYP3-2]
DR Antibodypedia; 24653; 81 antibodies from 20 providers.
DR DNASU; 54453; -.
DR Ensembl; ENST00000255006.12; ENSP00000255006.7; ENSG00000132669.14. [Q8WYP3-1]
DR Ensembl; ENST00000648440.1; ENSP00000498085.1; ENSG00000132669.14. [Q8WYP3-1]
DR GeneID; 54453; -.
DR KEGG; hsa:54453; -.
DR MANE-Select; ENST00000255006.12; ENSP00000255006.7; NM_018993.4; NP_061866.1.
DR UCSC; uc002wro.3; human. [Q8WYP3-1]
DR CTD; 54453; -.
DR DisGeNET; 54453; -.
DR GeneCards; RIN2; -.
DR HGNC; HGNC:18750; RIN2.
DR HPA; ENSG00000132669; Low tissue specificity.
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 VEuPathDB; HostDB:ENSG00000132669; -.
DR eggNOG; KOG2320; Eukaryota.
DR GeneTree; ENSGT00940000154866; -.
DR HOGENOM; CLU_011829_1_0_1; -.
DR InParanoid; Q8WYP3; -.
DR OMA; ACKDSRQ; -.
DR OrthoDB; 1311692at2759; -.
DR PhylomeDB; Q8WYP3; -.
DR TreeFam; TF331067; -.
DR PathwayCommons; Q8WYP3; -.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; Q8WYP3; -.
DR BioGRID-ORCS; 54453; 17 hits in 1074 CRISPR screens.
DR ChiTaRS; RIN2; human.
DR GenomeRNAi; 54453; -.
DR Pharos; Q8WYP3; Tbio.
DR PRO; PR:Q8WYP3; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q8WYP3; protein.
DR Bgee; ENSG00000132669; Expressed in choroid plexus epithelium and 204 other tissues.
DR ExpressionAtlas; Q8WYP3; baseline and differential.
DR Genevisible; Q8WYP3; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030139; C:endocytic vesicle; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0030695; F:GTPase regulator activity; NAS:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IBA:GO_Central.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:CACAO.
DR GO; GO:1904906; P:positive regulation of endothelial cell-matrix adhesion via fibronectin; IMP:CACAO.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; IMP:CACAO.
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; IPR045046; Vps9-like.
DR InterPro; IPR037191; VPS9_dom_sf.
DR PANTHER; PTHR23101; PTHR23101; 1.
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; Cytoplasm; Endocytosis; GTPase activation;
KW Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1..895
FT /note="Ras and Rab interactor 2"
FT /id="PRO_0000191320"
FT DOMAIN 97..190
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 618..757
FT /note="VPS9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00550"
FT DOMAIN 787..878
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT REGION 284..361
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 373..442
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 460..481
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 286..304
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 321..340
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D684"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D684"
FT MOD_RES 509
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18318008"
FT VAR_SEQ 1
FT /note="M -> MLDSFSQESTLPFREARKRTSFQPVQVWRNFTASQTTESPACSGASL
FT GEM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015145"
FT VARIANT 197
FT /note="S -> T (in dbSNP:rs3803981)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_024694"
FT VARIANT 643
FT /note="A -> T (in dbSNP:rs199603)"
FT /id="VAR_052945"
FT CONFLICT 192
FT /note="I -> V (in Ref. 3; AK094884)"
FT /evidence="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
