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Q8WYP3 (RIN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ras and Rab interactor 2
Alternative name(s):
Ras association domain family 4
Ras inhibitor JC265
Ras interaction/interference protein 2
Gene names
Name:RIN2
Synonyms:RASSF4
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length895 AA.
Sequence statusComplete.
Protein existenceEvidence 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

Involvement in disease

Defects in RIN2 are the cause of MACS syndrome (MACS) [MIM:613075]; also called macrocephaly alopecia cutis laxa and scoliosis syndrome. MACS is an autosomal-recessive inherited complex disorder of elastic tissue, characterized by sagging skin and occasionally by life-threatening visceral complications. Ref.7

Sequence similarities

Belongs to the RIN (Ras interaction/interference) family.

Contains 1 Ras-associating domain.

Contains 1 SH2 domain.

Contains 1 VPS9 domain.

Sequence caution

The sequence CAB66858.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSH2 domain
   Molecular functionGTPase activation
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological processendocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

small GTPase mediated signal transduction

Non-traceable author statement Ref.5. Source: UniProtKB

   Cellular componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionGTPase activator activity

Inferred from electronic annotation. Source: UniProtKB-KW

Rab guanyl-nucleotide exchange factor activity

Non-traceable author statement Ref.1. Source: UniProtKB

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 895895Ras and Rab interactor 2
PRO_0000191320

Regions

Domain97 – 19094SH2
Domain618 – 757140VPS9
Domain787 – 87892Ras-associating
Compositional bias307 – 3148Poly-Pro

Amino acid modifications

Modified residue3661Phosphoserine By similarity
Modified residue5011Phosphoserine By similarity
Modified residue5091Phosphothreonine Ref.6

Natural variations

Alternative sequence11M → MLDSFSQESTLPFREARKRT SFQPVQVWRNFTASQTTESP ACSGASLGEM in isoform 2.
VSP_015145
Natural variant1971S → T. Ref.3
Corresponds to variant rs3803981 [ dbSNP | Ensembl ].
VAR_024694
Natural variant6431A → T.
Corresponds to variant rs199603 [ dbSNP | Ensembl ].
VAR_052945

Experimental info

Sequence conflict1921I → V in AK094884. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2002. Version 1.
Checksum: 0DECDBF8D2629EE4

FASTA895100,163
        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 

« Hide

Isoform 2 [UniParc].

Checksum: EB0C72971CE5BFB6
Show »

FASTA944105,613

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
[7]"RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome."
Basel-Vanagaite L., Sarig O., Hershkovitz D., Fuchs-Telem D., Rapaport D., Gat A., Isman G., Shirazi I., Shohat M., Enk C.D., Birk E., Kohlhase J., Matysiak-Scholze U., Maya I., Knopf C., Peffekoven A., Hennies H.-C., Bergman R. expand/collapse author list , Horowitz M., Ishida-Yamamoto A., Sprecher E.
Am. J. Hum. Genet. 85:254-263(2009) [PubMed: 19631308] [Abstract]
Cited for: INVOLVEMENT IN MACS SYNDROME.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
IPIIPI00103752.
IPI00549715.
PIRB38637.
RefSeqNP_001229510.1. NM_001242581.1.
NP_061866.1. NM_018993.3.
UniGeneHs.472270.

3D structure databases

ProteinModelPortalQ8WYP3.
SMRQ8WYP3. Positions 97-178.
ModBaseSearch...

Protein-protein interaction databases

IntActQ8WYP3. 1 interaction.
MINTMINT-1493616.
STRINGQ8WYP3.

PTM databases

PhosphoSiteQ8WYP3.

Polymorphism databases

DMDM28201876.

Proteomic databases

PRIDEQ8WYP3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000255006; ENSP00000255006; ENSG00000132669.
GeneID54453.
KEGGhsa:54453.
UCSCuc002wro.1. human.

Organism-specific databases

CTD54453.
GeneCardsGC20P019818.
H-InvDBHIX0015677.
HGNCHGNC:18750. RIN2.
HPAHPA034641.
MIM610222. gene.
613075. phenotype.
neXtProtNX_Q8WYP3.
Orphanet217335. MACS syndrome.
PharmGKBPA38672.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG11844.
GeneTreeENSGT00530000063053.
HOVERGENHBG023719.
InParanoidQ8WYP3.
OMATVNHNKH.
OrthoDBEOG46DM2M.

Gene expression databases

ArrayExpressQ8WYP3.
BgeeQ8WYP3.
CleanExHS_RASSF4.
HS_RIN2.
GenevestigatorQ8WYP3.
GermOnlineENSG00000132669. Homo sapiens.

Family and domain databases

InterProIPR000159. Ras-assoc.
IPR000980. SH2.
IPR003123. VPS9.
IPR013995. VPS9_subgr.
[Graphical view]
Gene3DG3DSA:3.30.505.10. SH2. 1 hit.
PfamPF00788. RA. 1 hit.
PF02204. VPS9. 1 hit.
[Graphical view]
SMARTSM00314. RA. 1 hit.
SM00252. SH2. 1 hit.
SM00167. VPS9. 1 hit.
[Graphical view]
PROSITEPS50200. RA. 1 hit.
PS50001. SH2. 1 hit.
PS51205. VPS9. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio56681.
SOURCESearch...

Entry information

Entry nameRIN2_HUMAN
AccessionPrimary (citable) accession number: Q8WYP3
Secondary accession number(s): Q00425 expand/collapse secondary AC list , Q5TFT8, Q9BQL3, Q9H071
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 2003
Last sequence update: March 1, 2002
Last modified: December 14, 2011
This is version 80 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families