SPAT2_MOUSE
ID SPAT2_MOUSE Reviewed; 515 AA.
AC Q8K004; Q3TAH0; Q3UML2;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Spermatogenesis-associated protein 2 {ECO:0000303|PubMed:28701375, ECO:0000303|PubMed:29025062};
GN Name=Spata2 {ECO:0000303|PubMed:28701375, ECO:0000303|PubMed:29025062,
GN ECO:0000312|MGI:MGI:2146885};
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=NOD; TISSUE=Lung, and Spleen;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye {ECO:0000312|EMBL:AAH34597.1};
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 [4]
RP SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=29025062; DOI=10.1093/biolre/iox093;
RA Zhao J., Zhao J., Xu G., Wang Z., Gao J., Cui S., Liu J.;
RT "Deletion of Spata2 by CRISPR/Cas9n causes increased inhibin alpha
RT expression and attenuated fertility in male mice.";
RL Biol. Reprod. 97:497-513(2017).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=28701375; DOI=10.1101/gad.299776.117;
RA Wei R., Xu L.W., Liu J., Li Y., Zhang P., Shan B., Lu X., Qian L., Wu Z.,
RA Dong K., Zhu H., Pan L., Yuan J., Pan H.;
RT "SPATA2 regulates the activation of RIPK1 by modulating linear
RT ubiquitination.";
RL Genes Dev. 31:1162-1176(2017).
CC -!- FUNCTION: Bridging factor that mediates the recruitment of CYLD to the
CC LUBAC complex, thereby regulating TNF-alpha-induced necroptosis (By
CC similarity). Acts as a direct binding intermediate that bridges
CC RNF31/HOIP, the catalytic subunit of the LUBAC complex, and the
CC deubiquitinase (CYLD), thereby recruiting CYLD to the TNF-R1 signaling
CC complex (TNF-RSC) (By similarity). Required to activate the 'Met-
CC 1'- (linear) and 'Lys-63'-linked deubiquitinase activities of CYLD
CC (PubMed:28701375). Controls the kinase activity of RIPK1 and TNF-alpha-
CC induced necroptosis by promoting 'Met-1'-linked deubiquitination of
CC RIPK1 by CYLD (PubMed:28701375). {ECO:0000250|UniProtKB:Q9UM82,
CC ECO:0000269|PubMed:28701375}.
CC -!- SUBUNIT: Interacts (via the PIM motif) with RNF31/HOIP (via the PUB
CC domain); the interaction is direct. Interacts (via the PUB domain) with
CC CYLD; the interaction is direct. {ECO:0000250|UniProtKB:Q9UM82}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:29025062}. Nucleus
CC {ECO:0000250|UniProtKB:Q66HP6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8K004-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K004-2; Sequence=VSP_059905, VSP_059906;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in
CC testis, lung and intestine, and lower expression in brain, heart and
CC spleen (PubMed:28701375). Present at high level in Sertoli cells:
CC expressed from stage I to stage XII of the testis seminiferous
CC epithelium (at protein level) (PubMed:29025062).
CC {ECO:0000269|PubMed:28701375, ECO:0000269|PubMed:29025062}.
CC -!- DISRUPTION PHENOTYPE: Mice are fertile and healthy with no obvious
CC abnormalities in major organs in normal conditions (PubMed:29025062,
CC PubMed:28701375). Males however display a decreased fertility: they
CC show reduced testis size and sperm number (PubMed:29025062). The
CC proliferation of germ cells in the seminiferous tubules is decreased in
CC male gonads (PubMed:29025062). Impaired necroptosis: deficient cells
CC show resistance to RIPK1-dependent apoptosis and necroptosis and are
CC partially protected against RIPK1-independent apoptosis
CC (PubMed:28701375). {ECO:0000269|PubMed:28701375,
CC ECO:0000269|PubMed:29025062}.
CC -!- SIMILARITY: Belongs to the SPATA2 family. {ECO:0000305}.
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DR EMBL; AK051741; BAC34748.1; -; mRNA.
DR EMBL; AK144826; BAE26086.1; -; mRNA.
DR EMBL; AK156188; BAE33617.1; -; mRNA.
DR EMBL; AK162743; BAE37046.1; -; mRNA.
DR EMBL; AK170356; BAE41742.1; -; mRNA.
DR EMBL; AK171664; BAE42596.1; -; mRNA.
DR EMBL; AK171852; BAE42698.1; -; mRNA.
DR EMBL; AL589870; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034597; AAH34597.1; -; mRNA.
DR CCDS; CCDS17100.1; -. [Q8K004-1]
DR CCDS; CCDS89587.1; -. [Q8K004-2]
DR RefSeq; NP_739562.1; NM_170756.2. [Q8K004-1]
DR RefSeq; XP_006499647.1; XM_006499584.2. [Q8K004-1]
DR RefSeq; XP_006499649.1; XM_006499586.3. [Q8K004-1]
DR RefSeq; XP_017174138.1; XM_017318649.1. [Q8K004-1]
DR RefSeq; XP_017174139.1; XM_017318650.1. [Q8K004-1]
DR RefSeq; XP_017174140.1; XM_017318651.1. [Q8K004-1]
DR AlphaFoldDB; Q8K004; -.
DR SMR; Q8K004; -.
DR STRING; 10090.ENSMUSP00000057095; -.
DR iPTMnet; Q8K004; -.
DR PhosphoSitePlus; Q8K004; -.
DR EPD; Q8K004; -.
DR jPOST; Q8K004; -.
DR MaxQB; Q8K004; -.
DR PaxDb; Q8K004; -.
DR PRIDE; Q8K004; -.
DR ProteomicsDB; 334874; -. [Q8K004-1]
DR ProteomicsDB; 343391; -.
DR Antibodypedia; 28514; 207 antibodies from 20 providers.
DR DNASU; 263876; -.
DR Ensembl; ENSMUST00000057627; ENSMUSP00000057095; ENSMUSG00000047030. [Q8K004-1]
DR Ensembl; ENSMUST00000109211; ENSMUSP00000104834; ENSMUSG00000047030. [Q8K004-2]
DR GeneID; 263876; -.
DR KEGG; mmu:263876; -.
DR UCSC; uc008nzs.1; mouse. [Q8K004-1]
DR CTD; 9825; -.
DR MGI; MGI:2146885; Spata2.
DR VEuPathDB; HostDB:ENSMUSG00000047030; -.
DR eggNOG; ENOG502RR2T; Eukaryota.
DR GeneTree; ENSGT00530000063956; -.
DR HOGENOM; CLU_039585_0_0_1; -.
DR InParanoid; Q8K004; -.
DR OMA; RTHLAKE; -.
DR OrthoDB; 461395at2759; -.
DR PhylomeDB; Q8K004; -.
DR TreeFam; TF328840; -.
DR BioGRID-ORCS; 263876; 10 hits in 74 CRISPR screens.
DR ChiTaRS; Spata2; mouse.
DR PRO; PR:Q8K004; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8K004; protein.
DR Bgee; ENSMUSG00000047030; Expressed in ear vesicle and 222 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; ISO:MGI.
DR GO; GO:1990381; F:ubiquitin-specific protease binding; ISO:MGI.
DR GO; GO:0070266; P:necroptotic process; IMP:MGI.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:1990108; P:protein linear deubiquitination; IMP:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0060544; P:regulation of necroptotic process; IMP:UniProtKB.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0072520; P:seminiferous tubule development; IMP:MGI.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR InterPro; IPR029744; SPATA2.
DR PANTHER; PTHR15326:SF8; PTHR15326:SF8; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Necrosis; Nucleus; Reference proteome.
FT CHAIN 1..515
FT /note="Spermatogenesis-associated protein 2"
FT /id="PRO_0000445574"
FT DOMAIN 78..150
FT /note="PUB"
FT /evidence="ECO:0000255"
FT REGION 429..452
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 321..338
FT /note="PIM motif"
FT /evidence="ECO:0000250|UniProtKB:Q9UM82"
FT VAR_SEQ 403..414
FT /note="KPSAFPSKASVH -> PLLGVSHYRRSL (in isoform 2)"
FT /id="VSP_059905"
FT VAR_SEQ 415..515
FT /note="Missing (in isoform 2)"
FT /id="VSP_059906"
FT CONFLICT 501
FT /note="Q -> K (in Ref. 1; BAE42698)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 515 AA; 57812 MW; 52968FF8ABA4D206 CRC64;
MDTKYKDDLF RKYVQFHEGK VDTTPGNQQP GSDEYLRVAA ATLLSLHKVD PLYRFRLIQF
YEVVESSLRS LSSSSLSALH CAFSMLETMA INLFLFPWKK EFRSIKTYTG PFVYYVKSTL
LEKDIRAILR FMGYEPELGT VYKLKELVES LQVKMVSFEL FLAKVECEQM LGIHSQVKDK
GYSELDVVAE RKGSTEDARG CSDALRRRAE SREHLTTSMA RVALQKSASE RAAKDYYKPR
VTKPSRSVDA YDSYWESRKP PSKASLSLRK EPLAMDVGED LKDEIIRPSP SLLAMSSSPH
GSPDDLSSIS SINGLGLLRS TYFSTQDDVD LYTDSEPRAT YRRQDALRPD VWLVKNDTHP
IYHKRSPPTK ESALSKCQNC GLSCSSSLCQ RCDSVLVCPS ASKPSAFPSK ASVHDSLAHG
APMREKYVGH QTQGLDRLAP VHSKPKPSTT ATSRCGFCNR AGATNTCTQC SKVSCDACLG
AYHYDPCCRK SELHKFLPNS QLNYKSAPFS QLVYR
