C42S1_HUMAN
ID C42S1_HUMAN Reviewed; 79 AA.
AC Q9NRR8; D3DV12; Q9HB17; Q9NQR2;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=CDC42 small effector protein 1;
DE AltName: Full=CDC42-binding protein SCIP1;
DE AltName: Full=Small effector of CDC42 protein 1;
GN Name=CDC42SE1; Synonyms=SPEC1;
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), FUNCTION, SUBCELLULAR LOCATION,
RP INTERACTION WITH CDC42, AND MUTAGENESIS OF PRO-33; HIS-38; HIS-41; GLN-62
RP AND LYS-66.
RX PubMed=10816584; DOI=10.1074/jbc.m002832200;
RA Pirone D.M., Fukuhara S., Gutkind J.S., Burbelo P.D.;
RT "SPECs, small binding proteins for Cdc42.";
RL J. Biol. Chem. 275:22650-22656(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=11595176; DOI=10.1016/s0378-1119(01)00561-3;
RA Pirone D.M., Oberst M.D., Stylianou D., Burbelo P.D.;
RT "The genomic structure of the human SPEC1 gene reveals complex splicing and
RT close promoter proximity to the AF1q translocation gene.";
RL Gene 273:295-303(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-79 (ISOFORM 1).
RA Mitina O.V., Serebriiskii I.G., Chernoff J.;
RT "Cloning and characterization of a small, CRIB-containing, Cdc42-binding
RT protein.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PALMITOYLATION AT
RP CYS-10 AND CYS-11, AND MUTAGENESIS OF 10-CYS-CYS-11; PRO-33; HIS-38 AND
RP HIS-41.
RX PubMed=15840583; DOI=10.1074/jbc.m500128200;
RA Ching K.H., Kisailus A.E., Burbelo P.D.;
RT "The role of SPECs, small Cdc42-binding proteins, in F-actin accumulation
RT at the immunological synapse.";
RL J. Biol. Chem. 280:23660-23667(2005).
RN [8]
RP FUNCTION, AND PHOSPHOINOSITIDE-BINDING.
RX PubMed=17045588; DOI=10.1016/j.yexcr.2006.09.011;
RA Ching K.H., Kisailus A.E., Burbelo P.D.;
RT "Biochemical characterization of distinct regions of SPEC molecules and
RT their role in phagocytosis.";
RL Exp. Cell Res. 313:10-21(2007).
CC -!- FUNCTION: Probably involved in the organization of the actin
CC cytoskeleton by acting downstream of CDC42, inducing actin filament
CC assembly. Alters CDC42-induced cell shape changes. In activated T-
CC cells, may play a role in CDC42-mediated F-actin accumulation at the
CC immunological synapse. May play a role in early contractile events in
CC phagocytosis in macrophages. {ECO:0000269|PubMed:10816584,
CC ECO:0000269|PubMed:15840583, ECO:0000269|PubMed:17045588}.
CC -!- SUBUNIT: Interacts with CDC42 (in GTP-bound form). Interacts weakly
CC with RAC1 and not at all with RHOA. {ECO:0000269|PubMed:10816584}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cell membrane; Lipid-
CC anchor. Note=Recruited to the activated TCR prior actin polymerization.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q9NRR8-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta;
CC IsoId=Q9NRR8-2; Sequence=VSP_033717;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in T-
CC lymphocytes, dendritic and whole blood cells.
CC {ECO:0000269|PubMed:15840583}.
CC -!- DOMAIN: The CRIB domain mediates interaction with CDC42.
CC -!- SIMILARITY: Belongs to the CDC42SE/SPEC family. {ECO:0000305}.
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DR EMBL; AF187845; AAF87597.1; -; mRNA.
DR EMBL; AF286592; AAG17723.1; -; mRNA.
DR EMBL; AL590133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53477.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53478.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53479.1; -; Genomic_DNA.
DR EMBL; BC012796; AAH12796.2; -; mRNA.
DR EMBL; BC041604; AAH41604.1; -; mRNA.
DR EMBL; AF286041; AAF97248.1; -; mRNA.
DR CCDS; CCDS981.1; -. [Q9NRR8-1]
DR RefSeq; NP_001033796.1; NM_001038707.1. [Q9NRR8-1]
DR RefSeq; NP_064624.1; NM_020239.3. [Q9NRR8-1]
DR RefSeq; XP_016857336.1; XM_017001847.1. [Q9NRR8-1]
DR AlphaFoldDB; Q9NRR8; -.
DR BioGRID; 121215; 14.
DR IntAct; Q9NRR8; 5.
DR STRING; 9606.ENSP00000475845; -.
DR ChEMBL; CHEMBL3308925; -.
DR iPTMnet; Q9NRR8; -.
DR PhosphoSitePlus; Q9NRR8; -.
DR SwissPalm; Q9NRR8; -.
DR BioMuta; CDC42SE1; -.
DR DMDM; 74752924; -.
DR EPD; Q9NRR8; -.
DR jPOST; Q9NRR8; -.
DR MassIVE; Q9NRR8; -.
DR MaxQB; Q9NRR8; -.
DR PaxDb; Q9NRR8; -.
DR PeptideAtlas; Q9NRR8; -.
DR PRIDE; Q9NRR8; -.
DR ProteomicsDB; 82416; -. [Q9NRR8-1]
DR Antibodypedia; 34046; 10 antibodies from 9 providers.
DR DNASU; 56882; -.
DR Ensembl; ENST00000357235.6; ENSP00000349773.4; ENSG00000197622.13. [Q9NRR8-1]
DR Ensembl; ENST00000439374.6; ENSP00000475845.1; ENSG00000197622.13. [Q9NRR8-1]
DR Ensembl; ENST00000540998.5; ENSP00000445647.1; ENSG00000197622.13. [Q9NRR8-1]
DR GeneID; 56882; -.
DR KEGG; hsa:56882; -.
DR MANE-Select; ENST00000357235.6; ENSP00000349773.4; NM_020239.4; NP_064624.1.
DR UCSC; uc001ewo.4; human. [Q9NRR8-1]
DR CTD; 56882; -.
DR DisGeNET; 56882; -.
DR GeneCards; CDC42SE1; -.
DR HGNC; HGNC:17719; CDC42SE1.
DR HPA; ENSG00000197622; Low tissue specificity.
DR MIM; 619456; gene.
DR neXtProt; NX_Q9NRR8; -.
DR OpenTargets; ENSG00000197622; -.
DR PharmGKB; PA134875001; -.
DR VEuPathDB; HostDB:ENSG00000197622; -.
DR eggNOG; ENOG502S499; Eukaryota.
DR GeneTree; ENSGT00940000160112; -.
DR HOGENOM; CLU_173417_1_0_1; -.
DR InParanoid; Q9NRR8; -.
DR OMA; DRPWNNS; -.
DR OrthoDB; 1646014at2759; -.
DR PhylomeDB; Q9NRR8; -.
DR TreeFam; TF323815; -.
DR PathwayCommons; Q9NRR8; -.
DR SignaLink; Q9NRR8; -.
DR BioGRID-ORCS; 56882; 65 hits in 1073 CRISPR screens.
DR ChiTaRS; CDC42SE1; human.
DR GenomeRNAi; 56882; -.
DR Pharos; Q9NRR8; Tdark.
DR PRO; PR:Q9NRR8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NRR8; protein.
DR Bgee; ENSG00000197622; Expressed in granulocyte and 195 other tissues.
DR Genevisible; Q9NRR8; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005095; F:GTPase inhibitor activity; TAS:ProtInc.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 3.90.810.10; -; 1.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR036936; CRIB_dom_sf.
DR InterPro; IPR039056; SPEC.
DR PANTHER; PTHR13502; PTHR13502; 1.
DR PROSITE; PS50108; CRIB; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell shape; Cytoplasm; Cytoskeleton;
KW Lipoprotein; Membrane; Palmitate; Phagocytosis; Reference proteome.
FT CHAIN 1..79
FT /note="CDC42 small effector protein 1"
FT /id="PRO_0000334629"
FT DOMAIN 30..43
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT REGION 19..24
FT /note="Mediates phosphoinositide-binding"
FT REGION 48..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 10
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:15840583"
FT LIPID 11
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:15840583"
FT VAR_SEQ 19..79
FT /note="KKKRRRIDRTMIGEPMNFVHLTHIGSGEMGAGDGLAMTGAVQEQMRSKGNRD
FT RPWSNSRGL -> VSLPTPHPNPKSSQLLCAVR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11595176"
FT /id="VSP_033717"
FT MUTAGEN 10..11
FT /note="CC->AA: Prevents targeting to the activated TCR."
FT /evidence="ECO:0000269|PubMed:15840583"
FT MUTAGEN 33
FT /note="P->A: Abolishes interaction with CDC42, induces a
FT decrease in blocking CDC42-induced JNK activation but does
FT not affect targeting to the activated TCR; when associated
FT with A-38 and A-41."
FT /evidence="ECO:0000269|PubMed:10816584,
FT ECO:0000269|PubMed:15840583"
FT MUTAGEN 38
FT /note="H->A: Abolishes interaction with CDC42, induces a
FT decrease in blocking CDC42-induced JNK activation but does
FT not affect targeting to the activated TCR; when associated
FT with A-33 and A-41."
FT /evidence="ECO:0000269|PubMed:10816584,
FT ECO:0000269|PubMed:15840583"
FT MUTAGEN 41
FT /note="H->A: Abolishes interaction with CDC42, induces a
FT decrease in blocking CDC42-induced JNK activation but does
FT not affect targeting to the activated TCR; when associated
FT with A-33 and A-38."
FT /evidence="ECO:0000269|PubMed:10816584,
FT ECO:0000269|PubMed:15840583"
FT MUTAGEN 62
FT /note="Q->A: Abolishes interaction with CDC42 and induces a
FT decrease in blocking CDC42-induced JNK activation; when
FT associated with A-66."
FT /evidence="ECO:0000269|PubMed:10816584"
FT MUTAGEN 66
FT /note="K->A: Abolishes interaction with CDC42 and induces a
FT decrease in blocking CDC42-induced JNK activation; when
FT associated with A-62."
FT /evidence="ECO:0000269|PubMed:10816584"
SQ SEQUENCE 79 AA; 8925 MW; D1C1DCEBD339EF5B CRC64;
MSEFWHKLGC CVVEKPQPKK KRRRIDRTMI GEPMNFVHLT HIGSGEMGAG DGLAMTGAVQ
EQMRSKGNRD RPWSNSRGL
