TB10C_HUMAN
ID TB10C_HUMAN Reviewed; 446 AA.
AC Q8IV04; G3V1D6;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Carabin;
DE AltName: Full=TBC1 domain family member 10C;
GN Name=TBC1D10C;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, Leukocyte, and Pancreas;
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 [4]
RP FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH CALCINEURIN AND HRAS, AND
RP MUTAGENESIS OF ARG-141.
RX PubMed=17230191; DOI=10.1038/nature05476;
RA Pan F., Sun L., Kardian D.B., Whartenby K.A., Pardoll D.M., Liu J.O.;
RT "Feedback inhibition of calcineurin and Ras by a dual inhibitory protein
RT Carabin.";
RL Nature 445:433-436(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
CC -!- FUNCTION: Inhibits the Ras signaling pathway through its intrinsic Ras
CC GTPase-activating protein (GAP) activity. Acts as a negative feedback
CC inhibitor of the calcineurin signaling pathway that also mediates
CC crosstalk between calcineurin and Ras. {ECO:0000269|PubMed:17230191}.
CC -!- SUBUNIT: Interacts with both calcineurin and HRAS.
CC {ECO:0000269|PubMed:17230191}.
CC -!- INTERACTION:
CC Q8IV04; P49639: HOXA1; NbExp=6; IntAct=EBI-10261452, EBI-740785;
CC Q8IV04; Q53G59: KLHL12; NbExp=6; IntAct=EBI-10261452, EBI-740929;
CC Q8IV04; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-10261452, EBI-3958099;
CC Q8IV04; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-10261452, EBI-945833;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IV04-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IV04-2; Sequence=VSP_045992, VSP_045993;
CC -!- TISSUE SPECIFICITY: Most abundant in spleen and peripheral blood
CC leukocytes. {ECO:0000269|PubMed:17230191}.
CC -!- DOMAIN: The arginine and glutamine fingers are critical for the GTPase-
CC activating mechanism, they pull out Rab's 'switch 2' glutamine and
CC insert in Rab's active site. {ECO:0000250}.
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DR EMBL; AP003419; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74613.1; -; Genomic_DNA.
DR EMBL; BC035630; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC036873; AAH36873.3; -; mRNA.
DR EMBL; BC062999; AAH62999.1; -; mRNA.
DR CCDS; CCDS58150.1; -. [Q8IV04-2]
DR CCDS; CCDS8162.1; -. [Q8IV04-1]
DR RefSeq; NP_001243437.1; NM_001256508.1. [Q8IV04-2]
DR RefSeq; NP_940919.1; NM_198517.3. [Q8IV04-1]
DR RefSeq; XP_006718601.1; XM_006718538.3. [Q8IV04-1]
DR RefSeq; XP_006718602.1; XM_006718539.3. [Q8IV04-1]
DR RefSeq; XP_006718603.1; XM_006718540.3.
DR AlphaFoldDB; Q8IV04; -.
DR SMR; Q8IV04; -.
DR BioGRID; 131899; 9.
DR DIP; DIP-60264N; -.
DR IntAct; Q8IV04; 7.
DR STRING; 9606.ENSP00000443654; -.
DR iPTMnet; Q8IV04; -.
DR PhosphoSitePlus; Q8IV04; -.
DR BioMuta; TBC1D10C; -.
DR DMDM; 74728014; -.
DR EPD; Q8IV04; -.
DR jPOST; Q8IV04; -.
DR MassIVE; Q8IV04; -.
DR MaxQB; Q8IV04; -.
DR PaxDb; Q8IV04; -.
DR PeptideAtlas; Q8IV04; -.
DR PRIDE; Q8IV04; -.
DR ProteomicsDB; 32335; -.
DR ProteomicsDB; 70638; -. [Q8IV04-1]
DR Antibodypedia; 30378; 141 antibodies from 24 providers.
DR DNASU; 374403; -.
DR Ensembl; ENST00000312390.9; ENSP00000310193.6; ENSG00000175463.12. [Q8IV04-2]
DR Ensembl; ENST00000526387.5; ENSP00000435543.1; ENSG00000175463.12. [Q8IV04-2]
DR Ensembl; ENST00000542590.2; ENSP00000443654.1; ENSG00000175463.12. [Q8IV04-1]
DR GeneID; 374403; -.
DR KEGG; hsa:374403; -.
DR MANE-Select; ENST00000542590.2; ENSP00000443654.1; NM_001369496.1; NP_001356425.1.
DR UCSC; uc001okz.5; human. [Q8IV04-1]
DR CTD; 374403; -.
DR GeneCards; TBC1D10C; -.
DR HGNC; HGNC:24702; TBC1D10C.
DR HPA; ENSG00000175463; Group enriched (bone marrow, intestine, lymphoid tissue).
DR MIM; 610831; gene.
DR neXtProt; NX_Q8IV04; -.
DR OpenTargets; ENSG00000175463; -.
DR PharmGKB; PA142670836; -.
DR VEuPathDB; HostDB:ENSG00000175463; -.
DR eggNOG; KOG2221; Eukaryota.
DR GeneTree; ENSGT00940000161287; -.
DR HOGENOM; CLU_857802_0_0_1; -.
DR InParanoid; Q8IV04; -.
DR OMA; QRMACPG; -.
DR OrthoDB; 976276at2759; -.
DR PhylomeDB; Q8IV04; -.
DR TreeFam; TF313293; -.
DR PathwayCommons; Q8IV04; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8854214; TBC/RABGAPs.
DR SignaLink; Q8IV04; -.
DR BioGRID-ORCS; 374403; 31 hits in 1070 CRISPR screens.
DR GenomeRNAi; 374403; -.
DR Pharos; Q8IV04; Tbio.
DR PRO; PR:Q8IV04; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8IV04; protein.
DR Bgee; ENSG00000175463; Expressed in granulocyte and 108 other tissues.
DR ExpressionAtlas; Q8IV04; baseline and differential.
DR Genevisible; Q8IV04; HS.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR GO; GO:0031527; C:filopodium membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0042113; P:B cell activation; IEA:Ensembl.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0050869; P:negative regulation of B cell activation; IEA:Ensembl.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR InterPro; IPR000195; Rab-GTPase-TBC_dom.
DR InterPro; IPR035969; Rab-GTPase_TBC_sf.
DR Pfam; PF00566; RabGAP-TBC; 1.
DR SMART; SM00164; TBC; 1.
DR SUPFAM; SSF47923; SSF47923; 2.
DR PROSITE; PS50086; TBC_RABGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; GTPase activation; Reference proteome.
FT CHAIN 1..446
FT /note="Carabin"
FT /id="PRO_0000284467"
FT DOMAIN 92..280
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT REGION 1..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 384..446
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 406..446
FT /note="Interaction with calcineurin"
FT SITE 137
FT /note="Arginine finger"
FT /evidence="ECO:0000250"
FT SITE 178
FT /note="Glutamine finger"
FT /evidence="ECO:0000250"
FT VAR_SEQ 157..310
FT /note="QQGLLQVLKAYTLYRPEQGYCQAQGPVAAVLLMHLPPEEAFWCLVQICEVYL
FT PGYYGPHMEAVRLDAEVFMALLRRLLPHVHKHLQQVGVGPLLYLPEWFLCLFARSLPFP
FT TVLRVWDAFLSEGARVLFRVGLTLVRLALGTAEQRGACPGLLE -> RGSCRCSRPTPC
FT IDRSRATARPRGPWLLCCSCTCPQRRPSGAWCRSVRSTSLGTTGPTWCQSTVPCGADTG
FT APGAGHCRAARGLPWPPGDTGSPSSHPPRAAAGGGLHVTGAQRGAVRAGPAAGDQGPAG
FT PAARFRAGTPAPATGPPRRGPSHL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045992"
FT VAR_SEQ 311..446
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045993"
FT MUTAGEN 141
FT /note="R->A: Loss of GAP activity."
FT /evidence="ECO:0000269|PubMed:17230191"
SQ SEQUENCE 446 AA; 49712 MW; 3ADD1D4C8CDBA1D7 CRC64;
MAQALGEDLV QPPELQDDSS SLGSDSELSG PGPYRQADRY GFIGGSSAEP GPGHPPADLI
RQREMKWVEM TSHWEKTMSR RYKKVKMQCR KGIPSALRAR CWPLLCGAHV CQKNSPGTYQ
ELAEAPGDPQ WMETIGRDLH RQFPLHEMFV SPQGHGQQGL LQVLKAYTLY RPEQGYCQAQ
GPVAAVLLMH LPPEEAFWCL VQICEVYLPG YYGPHMEAVR LDAEVFMALL RRLLPHVHKH
LQQVGVGPLL YLPEWFLCLF ARSLPFPTVL RVWDAFLSEG ARVLFRVGLT LVRLALGTAE
QRGACPGLLE TLGALRAIPP AQLQEEAFMS QVHSVVLSER DLQREIKAQL AQLPDSAPGP
PPRPQVRLAG AQAIFEAQQL AGVRRGAKPE VPRIVVQPPE EPRPPRRKPQ TRGKTFHGLL
TRARGPPIEG PPRPQRGSTS FLDTRF
