TBC21_MOUSE
ID TBC21_MOUSE Reviewed; 336 AA.
AC Q9D9D3; B7ZNH3;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=TBC1 domain family member 21 {ECO:0000312|MGI:MGI:1921536};
DE AltName: Full=Male germ cell Rab GTPase-activating protein {ECO:0000303|PubMed:21128978};
GN Name=Tbc1d21 {ECO:0000312|MGI:MGI:1921536};
GN Synonyms=MgcRabGAP {ECO:0000303|PubMed:21128978};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:AAI45240.1};
RN [1] {ECO:0000312|EMBL:BAB24855.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB24855.1};
RC TISSUE=Testis {ECO:0000312|EMBL:BAB24855.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3] {ECO:0000312|EMBL:EDL25950.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:AAI00469.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis {ECO:0000312|EMBL:AAI00469.1};
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 [5] {ECO:0000305}
RP FUNCTION, INTERACTION WITH ACTB, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DEVELOPMENTAL STAGE.
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 [6]
RP FUNCTION, INTERACTION WITH RAP1A, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=30360518; DOI=10.3390/ijms19113292;
RA Ke C.C., Lin Y.H., Wang Y.Y., Wu Y.Y., Chen M.F., Ku W.C., Chiang H.S.,
RA Lai T.H.;
RT "TBC1D21 Potentially Interacts with and Regulates Rap1 during Murine
RT Spermatogenesis.";
RL Int. J. Mol. Sci. 19:0-0(2018).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH TOMM20 AND DNAH7, AND
RP TISSUE SPECIFICITY.
RX PubMed=32976492; DOI=10.1371/journal.pgen.1009020;
RA Wang Y.Y., Ke C.C., Chen Y.L., Lin Y.H., Yu I.S., Ku W.C., O'Bryan M.K.,
RA Lin Y.H.;
RT "Deficiency of the Tbc1d21 gene causes male infertility with morphological
RT abnormalities of the sperm mitochondria and flagellum in mice.";
RL PLoS Genet. 16:e1009020-e1009020(2020).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH ARMC12, AND TISSUE
RP 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
CC (s) (PubMed:30360518). Essential for the establishment of male
CC fertility, and is required for both the production of normal sperm
CC number and sperm function (PubMed:32976492). Plays an important role in
CC the formation of intact mitochondria, outer dense fibers and axoneme
CC within the sperm tail (PubMed:32976492). Essential for sperm
CC mitochondrial sheath formation and for the interactions of ARMC12 with
CC VDAC2 and VDAC3 (PubMed:33536340). May be involved in acrosome
CC formation and cytoskeletal reorganization during spermiogenesis,
CC possibly by regulating RAB3A activity (PubMed:21128978).
CC {ECO:0000269|PubMed:30360518, ECO:0000269|PubMed:32976492,
CC ECO:0000269|PubMed:33536340, ECO:0000305|PubMed:21128978}.
CC -!- SUBUNIT: Interacts with ACTB (PubMed:21128978). Interacts with ARMC12
CC (PubMed:33536340). Interacts with TOMM20 and DNAH7 (PubMed:32976492).
CC Interacts with RAP1A (PubMed:30360518). Interacts with RAB10 (By
CC similarity). {ECO:0000250|UniProtKB:Q8IYX1,
CC ECO:0000269|PubMed:21128978, ECO:0000269|PubMed:30360518,
CC ECO:0000269|PubMed:32976492, ECO:0000269|PubMed:33536340}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, acrosome
CC {ECO:0000269|PubMed:21128978}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:21128978}. 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:0000269|PubMed:21128978}.
CC -!- TISSUE SPECIFICITY: Expressed in testis, specifically in elongating and
CC elongated spermatids (at protein level) (PubMed:21128978,
CC PubMed:30360518, PubMed:33536340). Expressed in the sperm midpiece (at
CC protein level) (PubMed:32976492, PubMed:33536340).
CC {ECO:0000269|PubMed:21128978, ECO:0000269|PubMed:30360518,
CC ECO:0000269|PubMed:32976492, ECO:0000269|PubMed:33536340}.
CC -!- DEVELOPMENTAL STAGE: Detected from postnatal day 35 onward.
CC {ECO:0000269|PubMed:21128978, ECO:0000269|PubMed:30360518}.
CC -!- DISRUPTION PHENOTYPE: Male mice are sterile, characterized by defects
CC in sperm tail structure and diminished sperm motility (PubMed:32976492,
CC PubMed:33536340). The mitochondria of the sperm-tail has an abnormal
CC irregular arrangement, abnormal diameter, and structural defects and
CC the axoneme structure of sperm tails is severely disturbed
CC (PubMed:32976492). Sperm mitochondria cannot form a proper
CC mitochondrial sheath at the subsequent mitochondrial compaction step,
CC although they can coil around the flagellum (PubMed:33536340).
CC {ECO:0000269|PubMed:32976492, ECO:0000269|PubMed:33536340}.
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DR EMBL; AK007086; BAB24855.1; -; mRNA.
DR EMBL; AC139320; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466522; EDL25950.1; -; Genomic_DNA.
DR EMBL; BC100468; AAI00469.1; -; mRNA.
DR EMBL; BC132329; AAI32330.1; -; mRNA.
DR EMBL; BC145239; AAI45240.1; -; mRNA.
DR EMBL; BC138332; AAI38333.1; -; mRNA.
DR CCDS; CCDS40655.1; -.
DR RefSeq; NP_083130.1; NM_028854.3.
DR AlphaFoldDB; Q9D9D3; -.
DR SMR; Q9D9D3; -.
DR STRING; 10090.ENSMUSP00000037525; -.
DR iPTMnet; Q9D9D3; -.
DR PhosphoSitePlus; Q9D9D3; -.
DR PaxDb; Q9D9D3; -.
DR PRIDE; Q9D9D3; -.
DR ProteomicsDB; 263131; -.
DR Antibodypedia; 26810; 264 antibodies from 20 providers.
DR Ensembl; ENSMUST00000040217; ENSMUSP00000037525; ENSMUSG00000036244.
DR GeneID; 74286; -.
DR KEGG; mmu:74286; -.
DR UCSC; uc009pww.1; mouse.
DR UCSC; uc012gun.1; mouse.
DR CTD; 161514; -.
DR MGI; MGI:1921536; Tbc1d21.
DR VEuPathDB; HostDB:ENSMUSG00000036244; -.
DR eggNOG; KOG2197; Eukaryota.
DR GeneTree; ENSGT00730000111374; -.
DR HOGENOM; CLU_071309_0_0_1; -.
DR InParanoid; Q9D9D3; -.
DR OMA; NIACDIQ; -.
DR OrthoDB; 1495285at2759; -.
DR PhylomeDB; Q9D9D3; -.
DR TreeFam; TF352573; -.
DR BioGRID-ORCS; 74286; 2 hits in 71 CRISPR screens.
DR PRO; PR:Q9D9D3; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9D9D3; protein.
DR Bgee; ENSMUSG00000036244; Expressed in spermatid and 6 other tissues.
DR ExpressionAtlas; Q9D9D3; baseline and differential.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:MGI.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0097225; C:sperm midpiece; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:MGI.
DR GO; GO:0005096; F:GTPase activator activity; ISS:UniProtKB.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:UniProtKB.
DR GO; GO:0007288; P:sperm axoneme assembly; IMP:UniProtKB.
DR GO; GO:0120317; P:sperm mitochondrial sheath assembly; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; 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 Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Differentiation;
KW GTPase activation; Reference proteome; Spermatogenesis.
FT CHAIN 1..336
FT /note="TBC1 domain family member 21"
FT /id="PRO_0000436614"
FT DOMAIN 57..265
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT CONFLICT 226..227
FT /note="KG -> R (in Ref. 4; AAI45240)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 336 AA; 39261 MW; C11AC9E8F99783DB CRC64;
MTTLSPENSL SARRSATFIL EKRNPPIDKA EWDSFFDENG HLAKSRDFIC INILERGLHP
FVRTEAWKFL TGYYSWQSSR DERLMVDSNR RRNYNSLCQM YEKIQPLLEN LHGNFTETRN
NIAYDIQRLY DKDPLGNVLI DKKKLEKTLL LSYVCNTKAE YQRGFHEMVM LFQLMVEHDH
ETFWLFQFFL QKTEHSCVIN IGVGKNLDML NSLITLLDPE FAEHLKGKGS GAVQSLFPWF
CLCFQRAFKT FDDVWRLWEV LLTGKPCRNF QVLVAYSMLQ MVREQALLEC MSGDAILMAC
NNLIDLDADE LISAACVVYS ELMQKEVPQP LKEFLL
