TBC21_HUMAN
ID TBC21_HUMAN Reviewed; 336 AA.
AC Q8IYX1; B9A6M2;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=TBC1 domain family member 21;
DE AltName: Full=Male germ cell Rab GTPase-activating protein {ECO:0000303|PubMed:28067790};
GN Name=TBC1D21; Synonyms=MGCRABGAP {ECO:0000303|PubMed:28067790};
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 2), AND PROPOSED FUNCTION.
RC TISSUE=Brain;
RX PubMed=19077034; DOI=10.1111/j.1365-2443.2008.01251.x;
RA Ishibashi K., Kanno E., Itoh T., Fukuda M.;
RT "Identification and characterization of a novel Tre-2/Bub2/Cdc16 (TBC)
RT protein that possesses Rab3A-GAP activity.";
RL Genes Cells 14:41-52(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 PROPOSED FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21128978; DOI=10.1111/j.1365-2605.2010.01126.x;
RA Lin Y.H., Lin Y.M., Kuo Y.C., Wang Y.Y., Kuo P.L.;
RT "Identification and characterization of a novel Rab GTPase-activating
RT protein in spermatids.";
RL Int. J. Androl. 34:E358-E367(2011).
RN [5]
RP FUNCTION, INTERACTION WITH RAB10, AND TISSUE SPECIFICITY.
RX PubMed=28067790; DOI=10.3390/ijms18010097;
RA Lin Y.H., Ke C.C., Wang Y.Y., Chen M.F., Chen T.M., Ku W.C., Chiang H.S.,
RA Yeh C.H.;
RT "RAB10 Interacts with the Male Germ Cell-Specific GTPase-Activating Protein
RT during Mammalian Spermiogenesis.";
RL Int. J. Mol. Sci. 18:0-0(2017).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=33536340; DOI=10.1073/pnas.2018355118;
RA Shimada K., Park S., Miyata H., Yu Z., Morohoshi A., Oura S., Matzuk M.M.,
RA Ikawa M.;
RT "ARMC12 regulates spatiotemporal mitochondrial dynamics during
RT spermiogenesis and is required for male fertility.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
CC -!- FUNCTION: Acts as a GTPase-activating protein for Rab family protein(s)
CC (PubMed:28067790, PubMed:19077034). Essential for the establishment of
CC male fertility, and is required for both the production of normal sperm
CC number and sperm function (By similarity). Plays an important role in
CC the formation of intact mitochondria, outer dense fibers and axoneme
CC within the sperm tail (By similarity). Essential for sperm
CC mitochondrial sheath formation and for the interactions of ARMC12 with
CC VDAC2 and VDAC3 (By similarity). May be involved in acrosome formation
CC and cytoskeletal reorganization during spermiogenesis, possibly by
CC regulating RAB3A activity (PubMed:21128978).
CC {ECO:0000250|UniProtKB:Q9D9D3, ECO:0000269|PubMed:28067790,
CC ECO:0000305|PubMed:19077034, ECO:0000305|PubMed:21128978}.
CC -!- SUBUNIT: Interacts with ACTB (By similarity). Interacts with ARMC12,
CC TOMM20, DNAH7 and RAP1A (By similarity). Interacts with RAB10
CC (PubMed:28067790). {ECO:0000250|UniProtKB:Q9D9D3,
CC ECO:0000269|PubMed:28067790}.
CC -!- INTERACTION:
CC Q8IYX1; Q96M91: CFAP53; NbExp=3; IntAct=EBI-12018146, EBI-742422;
CC Q8IYX1; Q96CN4: EVI5L; NbExp=3; IntAct=EBI-12018146, EBI-749523;
CC Q8IYX1; O43903-2: GAS2; NbExp=5; IntAct=EBI-12018146, EBI-12952691;
CC Q8IYX1; P14136: GFAP; NbExp=6; IntAct=EBI-12018146, EBI-744302;
CC Q8IYX1; P29083: GTF2E1; NbExp=3; IntAct=EBI-12018146, EBI-5462215;
CC Q8IYX1; Q9ULI4: KIF26A; NbExp=9; IntAct=EBI-12018146, EBI-1642152;
CC Q8IYX1; P19012: KRT15; NbExp=3; IntAct=EBI-12018146, EBI-739566;
CC Q8IYX1; Q92764: KRT35; NbExp=3; IntAct=EBI-12018146, EBI-1058674;
CC Q8IYX1; O76014: KRT37; NbExp=3; IntAct=EBI-12018146, EBI-1045716;
CC Q8IYX1; O76015: KRT38; NbExp=5; IntAct=EBI-12018146, EBI-1047263;
CC Q8IYX1; Q6A162: KRT40; NbExp=3; IntAct=EBI-12018146, EBI-10171697;
CC Q8IYX1; P80188: LCN2; NbExp=3; IntAct=EBI-12018146, EBI-11911016;
CC Q8IYX1; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12018146, EBI-16439278;
CC Q8IYX1; Q6NSM0: NR1D2; NbExp=3; IntAct=EBI-12018146, EBI-10250949;
CC Q8IYX1; Q16342: PDCD2; NbExp=3; IntAct=EBI-12018146, EBI-359462;
CC Q8IYX1; Q6P1K2: PMF1; NbExp=3; IntAct=EBI-12018146, EBI-713832;
CC Q8IYX1; Q6P1K2-3: PMF1; NbExp=3; IntAct=EBI-12018146, EBI-12906008;
CC Q8IYX1; Q96QF0-7: RAB3IP; NbExp=3; IntAct=EBI-12018146, EBI-11984839;
CC Q8IYX1; Q04864-2: REL; NbExp=3; IntAct=EBI-12018146, EBI-10829018;
CC Q8IYX1; Q8N443: RIBC1; NbExp=3; IntAct=EBI-12018146, EBI-10265323;
CC Q8IYX1; Q9UPU9-3: SAMD4A; NbExp=3; IntAct=EBI-12018146, EBI-11986417;
CC Q8IYX1; Q15019-3: SEPTIN2; NbExp=3; IntAct=EBI-12018146, EBI-11525407;
CC Q8IYX1; Q9UNH6-3: SNX7; NbExp=3; IntAct=EBI-12018146, EBI-12424584;
CC Q8IYX1; Q9NZ72: STMN3; NbExp=3; IntAct=EBI-12018146, EBI-725557;
CC Q8IYX1; Q99081-3: TCF12; NbExp=3; IntAct=EBI-12018146, EBI-11952764;
CC Q8IYX1; P62072: TIMM10; NbExp=3; IntAct=EBI-12018146, EBI-1200391;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, acrosome
CC {ECO:0000250|UniProtKB:Q9D9D3}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q9D9D3}. Note=Located at the edge of the
CC acrosomal region, neck and annulus during spermiogenesis. Colocalizes
CC with RAB3A at the acrosome-acroplaxome and neck regions of spermatids.
CC Colocalizes with ACTB at the neck region in elongated spermatids.
CC {ECO:0000250|UniProtKB:Q9D9D3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IYX1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IYX1-2; Sequence=VSP_053999;
CC -!- TISSUE SPECIFICITY: Expressed in round and elongated spermatids (at
CC protein level). Expressed specifically in adult testis and very weakly
CC in fetal brain. {ECO:0000269|PubMed:21128978,
CC ECO:0000269|PubMed:33536340}.
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; AB449907; BAH16650.1; -; mRNA.
DR EMBL; AC018943; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108137; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC033516; AAH33516.1; -; mRNA.
DR CCDS; CCDS10252.1; -. [Q8IYX1-1]
DR CCDS; CCDS66822.1; -. [Q8IYX1-2]
DR RefSeq; NP_001273363.1; NM_001286434.1. [Q8IYX1-2]
DR RefSeq; NP_699187.1; NM_153356.2. [Q8IYX1-1]
DR AlphaFoldDB; Q8IYX1; -.
DR SMR; Q8IYX1; -.
DR BioGRID; 127795; 34.
DR IntAct; Q8IYX1; 25.
DR STRING; 9606.ENSP00000300504; -.
DR GlyGen; Q8IYX1; 1 site, 1 O-linked glycan (1 site).
DR PhosphoSitePlus; Q8IYX1; -.
DR BioMuta; TBC1D21; -.
DR DMDM; 59798963; -.
DR MassIVE; Q8IYX1; -.
DR PaxDb; Q8IYX1; -.
DR PeptideAtlas; Q8IYX1; -.
DR PRIDE; Q8IYX1; -.
DR ProteomicsDB; 71255; -. [Q8IYX1-1]
DR ProteomicsDB; 7518; -.
DR Antibodypedia; 26810; 264 antibodies from 20 providers.
DR DNASU; 161514; -.
DR Ensembl; ENST00000300504.7; ENSP00000300504.2; ENSG00000167139.9. [Q8IYX1-1]
DR Ensembl; ENST00000535547.6; ENSP00000439325.2; ENSG00000167139.9. [Q8IYX1-2]
DR GeneID; 161514; -.
DR KEGG; hsa:161514; -.
DR MANE-Select; ENST00000300504.7; ENSP00000300504.2; NM_153356.3; NP_699187.1.
DR UCSC; uc002avz.5; human. [Q8IYX1-1]
DR CTD; 161514; -.
DR DisGeNET; 161514; -.
DR GeneCards; TBC1D21; -.
DR HGNC; HGNC:28536; TBC1D21.
DR HPA; ENSG00000167139; Tissue enriched (testis).
DR neXtProt; NX_Q8IYX1; -.
DR OpenTargets; ENSG00000167139; -.
DR PharmGKB; PA134890585; -.
DR VEuPathDB; HostDB:ENSG00000167139; -.
DR eggNOG; KOG2197; Eukaryota.
DR GeneTree; ENSGT00730000111374; -.
DR InParanoid; Q8IYX1; -.
DR OMA; NIACDIQ; -.
DR OrthoDB; 1495285at2759; -.
DR PhylomeDB; Q8IYX1; -.
DR TreeFam; TF352573; -.
DR PathwayCommons; Q8IYX1; -.
DR SignaLink; Q8IYX1; -.
DR BioGRID-ORCS; 161514; 6 hits in 1054 CRISPR screens.
DR ChiTaRS; TBC1D21; human.
DR GenomeRNAi; 161514; -.
DR Pharos; Q8IYX1; Tdark.
DR PRO; PR:Q8IYX1; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q8IYX1; protein.
DR Bgee; ENSG00000167139; Expressed in right testis and 33 other tissues.
DR ExpressionAtlas; Q8IYX1; baseline and differential.
DR Genevisible; Q8IYX1; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0097225; C:sperm midpiece; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; IEA:Ensembl.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0030317; P:flagellated sperm motility; ISS:UniProtKB.
DR GO; GO:0007288; P:sperm axoneme assembly; ISS:UniProtKB.
DR GO; GO:0120317; P:sperm mitochondrial sheath assembly; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS: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; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW Differentiation; GTPase activation; Reference proteome; Spermatogenesis.
FT CHAIN 1..336
FT /note="TBC1 domain family member 21"
FT /id="PRO_0000208050"
FT DOMAIN 57..265
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT SITE 124
FT /note="Arginine finger"
FT /evidence="ECO:0000250"
FT SITE 163
FT /note="Glutamine finger"
FT /evidence="ECO:0000250"
FT VAR_SEQ 21..56
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:19077034"
FT /id="VSP_053999"
FT VARIANT 113
FT /note="R -> Q (in dbSNP:rs16958445)"
FT /id="VAR_034544"
SQ SEQUENCE 336 AA; 39221 MW; 2B459D2FDE843E20 CRC64;
MTTLSPENSL SARQSASFIL VKRKPPIDKT EWDSFFDESG HLAKSRDFIC VNILERGLHP
FVRTEAWKFL TGYFSWQSSQ DERLTVDSMR RKNYKALCQM YEKIQPLLEN LHRNFTETRN
NIARDIQKIY DKDPLGNVLI DKKRLEKILL LSYVCNTQAE YQQGFHEMMM LFQLMVEHDH
ETFWLFQFFL QKTEHSCVIN IGVAKNLDML STLITFLDPV FAEHLKGKGA GAVQSLFPWF
CFCFQRAFKS FDDVWRLWEV LLTGKPCRNF QVLVAYSMLQ MVREQVLQES MGGDDILLAC
NNLIDLDADE LISAACVVYA ELIQKDVPQT LKDFFL
