ID SPDYA_HUMAN Reviewed; 313 AA. AC Q5MJ70; Q53R05; Q5MJ69; DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 02-MAY-2006, sequence version 2. DT 24-JAN-2024, entry version 127. DE RecName: Full=Speedy protein A; DE AltName: Full=Rapid inducer of G2/M progression in oocytes A; DE Short=RINGO A; DE Short=hSpy/Ringo A; DE AltName: Full=Speedy-1; DE Short=Spy1; GN Name=SPDYA {ECO:0000312|HGNC:HGNC:30613}; GN Synonyms=SPDY1 {ECO:0000312|HGNC:HGNC:30613}, SPY1 GN {ECO:0000312|EMBL:AAY24014.1}; 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] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CDK2, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Testis {ECO:0000269|PubMed:11980914}; RX PubMed=11980914; DOI=10.1083/jcb.200109045; RA Porter L.A., Dellinger R.W., Tynan J.A., Barnes E.A., Kong M., RA Lenormand J.-L., Donoghue D.J.; RT "Human Speedy: a novel cell cycle regulator that enhances proliferation RT through activation of Cdk2."; RL J. Cell Biol. 157:357-366(2002). RN [2] {ECO:0000305, ECO:0000312|EMBL:AAW30395.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY. RC TISSUE=Testis {ECO:0000312|EMBL:AAW30394.1}; RX PubMed=15611625; DOI=10.4161/cc.4.1.1347; RA Cheng A., Xiong W., Ferrell J.E. Jr., Solomon M.J.; RT "Identification and comparative analysis of multiple mammalian Speedy/Ringo RT proteins."; RL Cell Cycle 4:155-165(2005). RN [3] {ECO:0000305, ECO:0000312|EMBL:AAY24014.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] {ECO:0000305, ECO:0000312|EMBL:AAH93005.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis {ECO:0000312|EMBL:AAH93005.1}; 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, AND INTERACTION WITH CDK2. RX PubMed=12839962; RA Barnes E.A., Porter L.A., Lenormand J.-L., Dellinger R.W., Donoghue D.J.; RT "Human Spy1 promotes survival of mammalian cells following DNA damage."; RL Cancer Res. 63:3701-3707(2003). RN [6] {ECO:0000305} RP FUNCTION, INTERACTION WITH CDKN1B, IDENTIFICATION IN A COMPLEX WITH CDKN1B RP AND CDK2, AND SUBCELLULAR LOCATION. RX PubMed=12972555; DOI=10.1091/mbc.e02-12-0820; RA Porter L.A., Kong-Beltran M., Donoghue D.J.; RT "Spy1 interacts with p27Kip1 to allow G1/S progression."; RL Mol. Biol. Cell 14:3664-3674(2003). RN [7] {ECO:0007744|PDB:5UQ1, ECO:0007744|PDB:5UQ2, ECO:0007744|PDB:5UQ3} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 61-213 IN COMPLEXES WITH CDK2 AND RP CDKN1B, SUBUNIT, FUNCTION, INTERACTION WITH CDK2, REGION, AND MUTAGENESIS RP OF ASP-97 AND GLU-135. RX PubMed=28666995; DOI=10.15252/embj.201796905; RA McGrath D.A., Fifield B.A., Marceau A.H., Tripathi S., Porter L.A., RA Rubin S.M.; RT "Structural basis of divergent cyclin-dependent kinase activation by RT Spy1/RINGO proteins."; RL EMBO J. 36:2251-2262(2017). CC -!- FUNCTION: Regulates the G1/S phase transition of the cell cycle by CC binding and activating CDK1 and CDK2 (PubMed:12972555). Contributes to CC CDK2 activation without promoting CDK2 phosphorylation, by inducing a CC conformation change of the CDK2 T-loop that obstructs the substrate- CC binding cleft prior to kinase activation (PubMed:28666995). Mediates CC cell survival during the DNA damage process through activation of CDK2 CC (PubMed:12839962). {ECO:0000269|PubMed:11980914, CC ECO:0000269|PubMed:12839962, ECO:0000269|PubMed:12972555, CC ECO:0000269|PubMed:28666995}. CC -!- SUBUNIT: Interacts with CDK1 (By similarity). Interacts with CDK2 CC (PubMed:11980914, PubMed:12839962, PubMed:12972555, PubMed:28666995). CC May interact with CDKN1B/KIP1 (PubMed:12972555). Identified in a CC complex with CDK2 and CDKN1B/KIP1, where it interacts primarily with CC CDK2 (PubMed:12972555, PubMed:28666995). {ECO:0000250|UniProtKB:Q5IBH7, CC ECO:0000269|PubMed:11980914, ECO:0000269|PubMed:12839962, CC ECO:0000269|PubMed:12972555, ECO:0000269|PubMed:28666995}. CC -!- INTERACTION: CC Q5MJ70; P29972: AQP1; NbExp=3; IntAct=EBI-7125479, EBI-745213; CC Q5MJ70; Q00535: CDK5; NbExp=3; IntAct=EBI-7125479, EBI-1041567; CC Q5MJ70; P46527: CDKN1B; NbExp=3; IntAct=EBI-7125479, EBI-519280; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11980914, CC ECO:0000269|PubMed:12972555}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=2 {ECO:0000269|PubMed:15611625, ECO:0000269|PubMed:15815621}; CC Synonyms=A2 {ECO:0000269|PubMed:15611625}; CC IsoId=Q5MJ70-2; Sequence=Displayed; CC Name=1 {ECO:0000269|PubMed:15611625}; Synonyms=A1 CC {ECO:0000269|PubMed:15611625}; CC IsoId=Q5MJ70-1; Sequence=VSP_052027, VSP_052028; CC -!- TISSUE SPECIFICITY: Highly expressed in testis. Expressed at a low CC level in wide range of tissues including bone marrow, brain, heart, CC kidney, colon, liver, placenta, spleen, skeletal muscle, salivary CC gland, thyroid gland, thymus, trachea and uterus. Expressed at a CC slightly higher level in adrenal gland, cerebellum, small intestine, CC lung, prostate and trachea. Expression is cell cycle-dependent, being CC restricted to cells in G1/S phase. {ECO:0000269|PubMed:11980914, CC ECO:0000269|PubMed:15611625}. CC -!- DOMAIN: The C-terminus is required for CDK2-activation, but not CDK2- CC binding. {ECO:0000250|UniProtKB:Q5IBH7}. CC -!- SIMILARITY: Belongs to the Speedy/Ringo family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY820303; AAW30394.1; -; mRNA. DR EMBL; AY820304; AAW30395.1; -; mRNA. DR EMBL; AC097720; AAY24014.1; -; Genomic_DNA. DR EMBL; BC093005; AAH93005.1; -; mRNA. DR CCDS; CCDS1767.2; -. [Q5MJ70-2] DR RefSeq; NP_001008779.1; NM_001008779.1. [Q5MJ70-1] DR RefSeq; NP_001136106.1; NM_001142634.1. [Q5MJ70-2] DR RefSeq; NP_877433.2; NM_182756.3. [Q5MJ70-2] DR PDB; 5UQ1; X-ray; 3.20 A; B/D=61-213. DR PDB; 5UQ2; X-ray; 2.70 A; B=61-213. DR PDB; 5UQ3; X-ray; 3.60 A; B=61-213. DR PDB; 7E34; X-ray; 3.19 A; B=61-213. DR PDBsum; 5UQ1; -. DR PDBsum; 5UQ2; -. DR PDBsum; 5UQ3; -. DR PDBsum; 7E34; -. DR AlphaFoldDB; Q5MJ70; -. DR SMR; Q5MJ70; -. DR BioGRID; 128828; 11. DR IntAct; Q5MJ70; 6. DR MINT; Q5MJ70; -. DR STRING; 9606.ENSP00000335628; -. DR iPTMnet; Q5MJ70; -. DR PhosphoSitePlus; Q5MJ70; -. DR BioMuta; SPDYA; -. DR DMDM; 94730574; -. DR MassIVE; Q5MJ70; -. DR PaxDb; 9606-ENSP00000335628; -. DR PeptideAtlas; Q5MJ70; -. DR ProteomicsDB; 63585; -. [Q5MJ70-2] DR ProteomicsDB; 63586; -. [Q5MJ70-1] DR Antibodypedia; 28865; 238 antibodies from 26 providers. DR DNASU; 245711; -. DR Ensembl; ENST00000334056.10; ENSP00000335628.5; ENSG00000163806.16. [Q5MJ70-2] DR Ensembl; ENST00000379579.8; ENSP00000368898.4; ENSG00000163806.16. [Q5MJ70-2] DR GeneID; 245711; -. DR KEGG; hsa:245711; -. DR MANE-Select; ENST00000334056.10; ENSP00000335628.5; NM_182756.4; NP_877433.2. DR UCSC; uc002rmj.4; human. [Q5MJ70-2] DR AGR; HGNC:30613; -. DR CTD; 245711; -. DR DisGeNET; 245711; -. DR GeneCards; SPDYA; -. DR HGNC; HGNC:30613; SPDYA. DR HPA; ENSG00000163806; Tissue enriched (testis). DR MIM; 614029; gene. DR neXtProt; NX_Q5MJ70; -. DR OpenTargets; ENSG00000163806; -. DR PharmGKB; PA134954857; -. DR VEuPathDB; HostDB:ENSG00000163806; -. DR eggNOG; KOG3938; Eukaryota. DR GeneTree; ENSGT00940000154524; -. DR HOGENOM; CLU_070353_1_2_1; -. DR InParanoid; Q5MJ70; -. DR OMA; VCQTPPT; -. DR OrthoDB; 3186118at2759; -. DR PhylomeDB; Q5MJ70; -. DR TreeFam; TF329827; -. DR PathwayCommons; Q5MJ70; -. DR SignaLink; Q5MJ70; -. DR SIGNOR; Q5MJ70; -. DR BioGRID-ORCS; 245711; 8 hits in 1148 CRISPR screens. DR ChiTaRS; SPDYA; human. DR GeneWiki; SPDYA; -. DR GenomeRNAi; 245711; -. DR Pharos; Q5MJ70; Tbio. DR PRO; PR:Q5MJ70; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q5MJ70; Protein. DR Bgee; ENSG00000163806; Expressed in left testis and 99 other cell types or tissues. DR ExpressionAtlas; Q5MJ70; baseline and differential. DR GO; GO:0000781; C:chromosome, telomeric region; IEA:Ensembl. DR GO; GO:0005635; C:nuclear envelope; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0001741; C:XY body; IEA:Ensembl. DR GO; GO:0030295; F:protein kinase activator activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0070200; P:establishment of protein localization to telomere; IEA:Ensembl. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IDA:UniProtKB. DR GO; GO:0007140; P:male meiotic nuclear division; ISS:UniProtKB. DR GO; GO:0070197; P:meiotic attachment of telomere to nuclear envelope; IEA:Ensembl. DR GO; GO:0048477; P:oogenesis; IEA:Ensembl. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:UniProtKB. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. DR GO; GO:0016233; P:telomere capping; IEA:Ensembl. DR InterPro; IPR020984; Speedy. DR PANTHER; PTHR31545; SEEDY PROTEIN A/C FAMILY MEMBER; 1. DR PANTHER; PTHR31545:SF4; SPEEDY PROTEIN A; 1. DR Pfam; PF11357; Spy1; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell cycle; Developmental protein; KW DNA damage; Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1..313 FT /note="Speedy protein A" FT /id="PRO_0000234112" FT REGION 68..200 FT /note="Speedy/Ringo box; Required for CDK-binding" FT /evidence="ECO:0000269|PubMed:28666995" FT REGION 278..313 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 288..313 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 222 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5IBH7" FT MOD_RES 224 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q5IBH7" FT VAR_SEQ 284..286 FT /note="VVN -> GMI (in isoform 1)" FT /evidence="ECO:0000303|PubMed:11980914, FT ECO:0000303|PubMed:15611625" FT /id="VSP_052027" FT VAR_SEQ 287..313 FT /note="Missing (in isoform 1)" FT /evidence="ECO:0000303|PubMed:11980914, FT ECO:0000303|PubMed:15611625" FT /id="VSP_052028" FT MUTAGEN 97 FT /note="D->N: Loss of CDK2 activation; when associated with FT Q-135." FT /evidence="ECO:0000269|PubMed:28666995" FT MUTAGEN 135 FT /note="E->Q: Loss of CDK2 activation; when associated with FT N-97." FT /evidence="ECO:0000269|PubMed:28666995" FT STRAND 64..67 FT /evidence="ECO:0007829|PDB:7E34" FT HELIX 72..75 FT /evidence="ECO:0007829|PDB:5UQ2" FT HELIX 76..79 FT /evidence="ECO:0007829|PDB:5UQ2" FT HELIX 81..89 FT /evidence="ECO:0007829|PDB:5UQ2" FT STRAND 94..96 FT /evidence="ECO:0007829|PDB:5UQ2" FT HELIX 98..110 FT /evidence="ECO:0007829|PDB:5UQ2" FT HELIX 115..117 FT /evidence="ECO:0007829|PDB:5UQ2" FT HELIX 120..134 FT /evidence="ECO:0007829|PDB:5UQ2" FT HELIX 140..143 FT /evidence="ECO:0007829|PDB:5UQ2" FT HELIX 144..149 FT /evidence="ECO:0007829|PDB:5UQ2" FT HELIX 150..152 FT /evidence="ECO:0007829|PDB:7E34" FT HELIX 153..155 FT /evidence="ECO:0007829|PDB:5UQ2" FT HELIX 157..170 FT /evidence="ECO:0007829|PDB:5UQ2" FT TURN 171..173 FT /evidence="ECO:0007829|PDB:5UQ2" FT HELIX 179..185 FT /evidence="ECO:0007829|PDB:5UQ2" FT STRAND 187..189 FT /evidence="ECO:0007829|PDB:5UQ1" FT HELIX 193..196 FT /evidence="ECO:0007829|PDB:5UQ2" SQ SEQUENCE 313 AA; 36463 MW; F511EECB26245EEC CRC64; MRHNQMCCET PPTVTVYVKS GSNRSHQPKK PITLKRPICK DNWQAFEKNT HNNNKSKRPK GPCLVIQRQD MTAFFKLFDD DLIQDFLWMD CCCKIADKYL LAMTFVYFKR AKFTISEHTR INFFIALYLA NTVEEDEEET KYEIFPWALG KNWRKLFPNF LKLRDQLWDR IDYRAIVSRR CCEEVMAIAP THYIWQRERS VHHSGAVRNY NRDEVQLPRG PSATPVDCSL CGKKRRYVRL GLSSSSSLSS HTAGVTEKHS QDSYNSLSMD IIGDPSQAYT GSEVVNDHQS NKGKKTNFLK KDKSMEWFTG SEE //