CD2AP_RAT
ID CD2AP_RAT Reviewed; 637 AA.
AC F1LRS8; Q7TSS5;
DT 22-JAN-2014, integrated into UniProtKB/Swiss-Prot.
DT 22-JAN-2014, sequence version 2.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=CD2-associated protein;
GN Name=Cd2ap;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kawachi H., Koike H., Shimizu F.;
RT "Rat CD2AP.";
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP FUNCTION IN RET STABILITY, INTERACTION WITH CBLC AND RET, AND TISSUE
RP SPECIFICITY.
RX PubMed=18753381; DOI=10.1523/jneurosci.2738-08.2008;
RA Tsui C.C., Pierchala B.A.;
RT "CD2AP and Cbl-3/Cbl-c constitute a critical checkpoint in the regulation
RT of ret signal transduction.";
RL J. Neurosci. 28:8789-8800(2008).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458; SER-469; SER-510 AND
RP SER-514, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Seems to act as an adapter protein between membrane proteins
CC and the actin cytoskeleton (By similarity). In collaboration with CBLC,
CC modulates the rate of RET turnover and may act as regulatory checkpoint
CC that limits the potency of GDNF on neuronal survival. Controls CBLC
CC function, converting it from an inhibitor to a promoter of RET
CC degradation (PubMed:18753381). May play a role in receptor clustering
CC and cytoskeletal polarity in the junction between T-cell and antigen-
CC presenting cell (By similarity). May anchor the podocyte slit diaphragm
CC to the actin cytoskeleton in renal glomerolus. Also required for
CC cytokinesis. Plays a role in epithelial cell junctions formation (By
CC similarity). {ECO:0000250|UniProtKB:Q9JLQ0,
CC ECO:0000250|UniProtKB:Q9Y5K6, ECO:0000269|PubMed:18753381}.
CC -!- SUBUNIT: Homodimer. Interacts with F-actin, PKD2, NPHS1 and NPHS2.
CC Interacts with WTIP. Interacts with DDN; interaction is direct.
CC Interacts (via SH3 2 domain) with CBL (via phosphorylated C-terminus).
CC Interacts with BCAR1/p130Cas (via SH3 domain). Interacts with MVB12A
CC and ARHGAP17. Interacts with ANLN, CD2 and CBLB. Interacts with PDCD6IP
CC and TSG101. Interacts with RIN3. Interacts directly with RET (inactive)
CC and CBLC; upon RET activation by GDNF suggested to dissociate from RET
CC as CBLC:CD2AP complex. Interacts with CGNL1 and SH3BP1; probably part
CC of a complex at cell junctions. Interacts with CAPZA1.
CC {ECO:0000250|UniProtKB:Q9Y5K6, ECO:0000269|PubMed:18753381,
CC ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q9Y5K6}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:Q9Y5K6}. Cell junction
CC {ECO:0000250|UniProtKB:Q9Y5K6}. Note=Colocalizes with F-actin and
CC BCAR1/p130Cas in membrane ruffles (By similarity). Located at podocyte
CC slit diaphragm between podocyte foot processes (By similarity). During
CC late anaphase and telophase, concentrates in the vicinity of the
CC midzone microtubules and in the midbody in late telophase (By
CC similarity). {ECO:0000250|UniProtKB:Q9JLQ0,
CC ECO:0000250|UniProtKB:Q9Y5K6}.
CC -!- TISSUE SPECIFICITY: Expressed in neurons and renal glomerular podocytes
CC (at protein level). {ECO:0000269|PubMed:18753381}.
CC -!- DOMAIN: The Pro-rich domain may mediate binding to SH3 domains.
CC {ECO:0000250}.
CC -!- DOMAIN: Potential homodimerization is mediated by the coiled coil
CC domain. {ECO:0000250}.
CC -!- PTM: Phosphorylated on tyrosine residues; probably by c-Abl, Fyn and c-
CC Src. {ECO:0000250}.
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DR EMBL; AY114147; AAM47029.1; -; mRNA.
DR EMBL; AABR06058949; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06058950; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06058951; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; F1LRS8; -.
DR SMR; F1LRS8; -.
DR CORUM; F1LRS8; -.
DR IntAct; F1LRS8; 1.
DR STRING; 10116.ENSRNOP00000016291; -.
DR iPTMnet; F1LRS8; -.
DR PhosphoSitePlus; F1LRS8; -.
DR jPOST; F1LRS8; -.
DR PaxDb; F1LRS8; -.
DR PRIDE; F1LRS8; -.
DR RGD; 727803; Cd2ap.
DR VEuPathDB; HostDB:ENSRNOG00000011987; -.
DR eggNOG; KOG4348; Eukaryota.
DR HOGENOM; CLU_024255_2_0_1; -.
DR InParanoid; F1LRS8; -.
DR OMA; RSPGTIY; -.
DR TreeFam; TF350191; -.
DR PRO; PR:F1LRS8; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000011987; Expressed in stomach and 18 other tissues.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0031252; C:cell leading edge; IDA:RGD.
DR GO; GO:0005911; C:cell-cell junction; ISO:RGD.
DR GO; GO:0034451; C:centriolar satellite; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0030425; C:dendrite; ISO:RGD.
DR GO; GO:0030139; C:endocytic vesicle; IDA:RGD.
DR GO; GO:0001650; C:fibrillar center; IEA:Ensembl.
DR GO; GO:0031941; C:filamentous actin; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0001726; C:ruffle; ISO:RGD.
DR GO; GO:0031982; C:vesicle; ISO:RGD.
DR GO; GO:0008013; F:beta-catenin binding; IDA:RGD.
DR GO; GO:0045296; F:cadherin binding; IPI:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0017124; F:SH3 domain binding; ISO:RGD.
DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; IDA:RGD.
DR GO; GO:0007015; P:actin filament organization; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; IMP:RGD.
DR GO; GO:0098609; P:cell-cell adhesion; IMP:RGD.
DR GO; GO:0051058; P:negative regulation of small GTPase mediated signal transduction; ISS:UniProtKB.
DR GO; GO:0032911; P:negative regulation of transforming growth factor beta1 production; ISO:RGD.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:RGD.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISO:RGD.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:RGD.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; ISO:RGD.
DR GO; GO:0048259; P:regulation of receptor-mediated endocytosis; IDA:RGD.
DR GO; GO:0032905; P:transforming growth factor beta1 production; IEA:Ensembl.
DR GO; GO:0016050; P:vesicle organization; IDA:RGD.
DR CDD; cd12053; SH3_CD2AP_1; 1.
DR CDD; cd12054; SH3_CD2AP_2; 1.
DR CDD; cd12056; SH3_CD2AP_3; 1.
DR InterPro; IPR028445; CD2AP.
DR InterPro; IPR035775; CD2AP_SH3_1.
DR InterPro; IPR035777; CD2AP_SH3_3.
DR InterPro; IPR035776; CD2AP_SH_2.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR14167:SF23; PTHR14167:SF23; 2.
DR Pfam; PF00018; SH3_1; 1.
DR Pfam; PF14604; SH3_9; 2.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00326; SH3; 3.
DR SUPFAM; SSF50044; SSF50044; 3.
DR PROSITE; PS50002; SH3; 3.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cell junction; Cell projection; Coiled coil;
KW Cytoplasm; Cytoskeleton; Isopeptide bond; Mitosis; Phosphoprotein;
KW Reference proteome; Repeat; SH3 domain; SH3-binding; Ubl conjugation.
FT CHAIN 1..637
FT /note="CD2-associated protein"
FT /id="PRO_0000424877"
FT DOMAIN 1..59
FT /note="SH3 1; truncated"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 108..167
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 269..330
FT /note="SH3 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 1..175
FT /note="Interaction with ANLN and localization to the
FT midbody"
FT /evidence="ECO:0000250"
FT REGION 167..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 333..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 488..556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 580..635
FT /evidence="ECO:0000255"
FT MOTIF 336..352
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 378..397
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 410..422
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 358..377
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 411..425
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 441..455
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 518..533
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5K6"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5K6"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5K6"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 510
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 514
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 580
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5K6"
FT CROSSLNK 58
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5K6"
FT CROSSLNK 523
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5K6"
FT CONFLICT 169
FT /note="D -> E (in Ref. 1; AAM47029)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="T -> S (in Ref. 1; AAM47029)"
FT /evidence="ECO:0000305"
FT CONFLICT 450
FT /note="E -> D (in Ref. 1; AAM47029)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 637 AA; 70491 MW; 772F9EDFF65BA19B CRC64;
MVDYIVEYDY DAVHDDELTI RVGEIIRNVK KLQEEGWLEG ELNGRRGMFP DNFVKEIKRE
TEPKDDNLPI KRERPGNVAS LVQRISTYGL PAGGIQPHPQ TKAMKKKTKK RQCKVLFEYS
PQNEDELELT VGDVIDVIEE VEEGWWSGTL NNKLGLFPSN FVKELESTDD GEMHDAQEES
EVSLTGPTSP MPSPGNGSEP APGSVTQPKK IRGVGFGDIF KEGSVKLRTR TSSSETEEKK
SEKPLILQSL GSRTQNVEVT KPDIDGKIKA KEYCKTVFPY TGTNEDELTF REGEIIHLIS
KETGEAGWWK GELNGKEGVF PDNFAVQISE LDKDFPKPKK PPPPAKGPAP KPDPLAGEKK
TFPLKAEDRD EKSLLEQKPS KPAAPQVPPK KPTPPTKANN LLRSPGTMYP KRPEKPVPPP
PPTAKINGEV STISSKIDTE PLSKPKLDPE QLPVRPKSVD LDALVARNSK ETDNVNFDDI
ASSENLLHLT ANRPKMPGRR LPGRFNGGHS PTQSPEKTLK LPKDDDSGNI KPSEFKKDAG
YSSKPSLSAP SSASKVNTAA FLSPLELKAK VEADDGKKSS LDELRAQIIE LLCIVDALKK
DHGKELEKLR RELEEEKAMR SNLEVEIAKL KKAVLLS
