SPIR2_HUMAN
ID SPIR2_HUMAN Reviewed; 714 AA.
AC Q8WWL2; A4QPB1; Q2TA98; Q6P433; Q8ND47; Q96JJ5;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Protein spire homolog 2;
DE Short=Spir-2;
GN Name=SPIRE2; Synonyms=KIAA1832, SPIR2;
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 1).
RA Kerkhoff E., Leberfinger C.B., Borawski J.M., Rapp U.R., Doerks T.,
RA Bork P.;
RT "The Drosophila spire gene is highly conserved between species.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Brain, and Skin;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 53-714 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-371 AND SER-442, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP FUNCTION.
RX PubMed=21620703; DOI=10.1016/j.cub.2011.04.029;
RA Pfender S., Kuznetsov V., Pleiser S., Kerkhoff E., Schuh M.;
RT "Spire-type actin nucleators cooperate with Formin-2 to drive asymmetric
RT oocyte division.";
RL Curr. Biol. 21:955-960(2011).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-371; SER-440; SER-442 AND
RP SER-476, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP FUNCTION.
RX PubMed=26287480; DOI=10.7554/elife.07735;
RA Belin B.J., Lee T., Mullins R.D.;
RT "DNA damage induces nuclear actin filament assembly by Formin -2 and Spire-
RT 1/2 that promotes efficient DNA repair.";
RL Elife 4:E07735-E07735(2015).
CC -!- FUNCTION: Acts as an actin nucleation factor, remains associated with
CC the slow-growing pointed end of the new filament (PubMed:21620703).
CC Involved in intracellular vesicle transport along actin fibers,
CC providing a novel link between actin cytoskeleton dynamics and
CC intracellular transport (By similarity). Required for asymmetric
CC spindle positioning and asymmetric cell division during meiosis
CC (PubMed:21620703). Required for normal formation of the cleavage furrow
CC and for polar body extrusion during female germ cell meiosis
CC (PubMed:21620703). Also acts in the nucleus: together with SPIRE1 and
CC SPIRE2, promotes assembly of nuclear actin filaments in response to DNA
CC damage in order to facilitate movement of chromatin and repair factors
CC after DNA damage (PubMed:26287480). {ECO:0000250|UniProtKB:Q8K1S6,
CC ECO:0000269|PubMed:21620703, ECO:0000269|PubMed:26287480}.
CC -!- INTERACTION:
CC Q8WWL2-2; O14964: HGS; NbExp=3; IntAct=EBI-10963872, EBI-740220;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q8K1S6}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q8K1S6}. Cell membrane
CC {ECO:0000250|UniProtKB:Q8K1S6}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8K1S6}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q8K1S6}. Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:Q8K1S6}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8K1S6}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q8K1S6}. Note=Detected at the cleavage furrow
CC during asymmetric oocyte division and polar body extrusion.
CC {ECO:0000250|UniProtKB:Q8K1S6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8WWL2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WWL2-2; Sequence=VSP_031572;
CC Name=3;
CC IsoId=Q8WWL2-3; Sequence=VSP_031569, VSP_031570;
CC Name=4;
CC IsoId=Q8WWL2-4; Sequence=VSP_031568, VSP_031571;
CC -!- DOMAIN: Binds to actin monomers via the WH2 domain.
CC {ECO:0000250|UniProtKB:Q9U1K1}.
CC -!- DOMAIN: The Spir-box targets binding to intracellular membrane
CC structures. {ECO:0000250|UniProtKB:Q08AE8}.
CC -!- SIMILARITY: Belongs to the spire family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB47461.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAD19439.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ422077; CAD19439.1; ALT_INIT; mRNA.
DR EMBL; AB058735; BAB47461.1; ALT_INIT; mRNA.
DR EMBL; BC063706; AAH63706.1; -; mRNA.
DR EMBL; BC111030; AAI11031.1; -; mRNA.
DR EMBL; BC139732; AAI39733.1; -; mRNA.
DR EMBL; AL834408; CAD39070.1; -; mRNA.
DR CCDS; CCDS32516.1; -. [Q8WWL2-1]
DR RefSeq; NP_115827.1; NM_032451.1. [Q8WWL2-1]
DR PDB; 5JCY; X-ray; 1.80 A; B=401-427.
DR PDBsum; 5JCY; -.
DR AlphaFoldDB; Q8WWL2; -.
DR SMR; Q8WWL2; -.
DR BioGRID; 124102; 17.
DR IntAct; Q8WWL2; 12.
DR STRING; 9606.ENSP00000367494; -.
DR DrugBank; DB08080; Latrunculin B.
DR iPTMnet; Q8WWL2; -.
DR PhosphoSitePlus; Q8WWL2; -.
DR BioMuta; SPIRE2; -.
DR DMDM; 296452951; -.
DR EPD; Q8WWL2; -.
DR jPOST; Q8WWL2; -.
DR MassIVE; Q8WWL2; -.
DR MaxQB; Q8WWL2; -.
DR PaxDb; Q8WWL2; -.
DR PeptideAtlas; Q8WWL2; -.
DR PRIDE; Q8WWL2; -.
DR ProteomicsDB; 74898; -. [Q8WWL2-1]
DR ProteomicsDB; 74899; -. [Q8WWL2-2]
DR ProteomicsDB; 74900; -. [Q8WWL2-3]
DR ProteomicsDB; 74901; -. [Q8WWL2-4]
DR Antibodypedia; 45052; 137 antibodies from 19 providers.
DR DNASU; 84501; -.
DR Ensembl; ENST00000378247.8; ENSP00000367494.3; ENSG00000204991.11. [Q8WWL2-1]
DR Ensembl; ENST00000393062.6; ENSP00000376782.2; ENSG00000204991.11. [Q8WWL2-2]
DR GeneID; 84501; -.
DR KEGG; hsa:84501; -.
DR MANE-Select; ENST00000378247.8; ENSP00000367494.3; NM_032451.2; NP_115827.1.
DR UCSC; uc002foz.2; human. [Q8WWL2-1]
DR CTD; 84501; -.
DR DisGeNET; 84501; -.
DR GeneCards; SPIRE2; -.
DR HGNC; HGNC:30623; SPIRE2.
DR HPA; ENSG00000204991; Tissue enhanced (pituitary).
DR MIM; 609217; gene.
DR neXtProt; NX_Q8WWL2; -.
DR OpenTargets; ENSG00000204991; -.
DR PharmGKB; PA134926582; -.
DR VEuPathDB; HostDB:ENSG00000204991; -.
DR eggNOG; ENOG502QQPN; Eukaryota.
DR GeneTree; ENSGT00390000003058; -.
DR HOGENOM; CLU_018839_1_1_1; -.
DR InParanoid; Q8WWL2; -.
DR OMA; QWMEFSH; -.
DR OrthoDB; 560461at2759; -.
DR PhylomeDB; Q8WWL2; -.
DR TreeFam; TF326239; -.
DR PathwayCommons; Q8WWL2; -.
DR SignaLink; Q8WWL2; -.
DR BioGRID-ORCS; 84501; 12 hits in 1088 CRISPR screens.
DR ChiTaRS; SPIRE2; human.
DR GenomeRNAi; 84501; -.
DR Pharos; Q8WWL2; Tbio.
DR PRO; PR:Q8WWL2; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q8WWL2; protein.
DR Bgee; ENSG00000204991; Expressed in pancreatic ductal cell and 154 other tissues.
DR ExpressionAtlas; Q8WWL2; baseline and differential.
DR Genevisible; Q8WWL2; HS.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR GO; GO:0032154; C:cleavage furrow; IEA:Ensembl.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0051639; P:actin filament network formation; IBA:GO_Central.
DR GO; GO:0030041; P:actin filament polymerization; IBA:GO_Central.
DR GO; GO:0045010; P:actin nucleation; IEA:InterPro.
DR GO; GO:0036089; P:cleavage furrow formation; ISS:UniProtKB.
DR GO; GO:0051295; P:establishment of meiotic spindle localization; IMP:UniProtKB.
DR GO; GO:0070649; P:formin-nucleated actin cable assembly; IMP:UniProtKB.
DR GO; GO:0048193; P:Golgi vesicle transport; IBA:GO_Central.
DR GO; GO:0046907; P:intracellular transport; ISS:UniProtKB.
DR GO; GO:0040038; P:polar body extrusion after meiotic divisions; ISS:UniProtKB.
DR GO; GO:2000781; P:positive regulation of double-strand break repair; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016192; P:vesicle-mediated transport; ISS:UniProtKB.
DR InterPro; IPR011019; KIND_dom.
DR InterPro; IPR029901; Spire.
DR InterPro; IPR029904; Spire2.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR PANTHER; PTHR21345; PTHR21345; 1.
DR PANTHER; PTHR21345:SF5; PTHR21345:SF5; 1.
DR Pfam; PF16474; KIND; 1.
DR SMART; SM00750; KIND; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS51377; KIND; 1.
DR PROSITE; PS51082; WH2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Cell membrane;
KW Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Membrane; Phosphoprotein;
KW Protein transport; Reference proteome; Repeat; Transport.
FT CHAIN 1..714
FT /note="Protein spire homolog 2"
FT /id="PRO_0000320023"
FT DOMAIN 22..203
FT /note="KIND"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00709"
FT DOMAIN 248..262
FT /note="WH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT DOMAIN 278..296
FT /note="WH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT DOMAIN 342..359
FT /note="WH2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT REGION 136..162
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 453..516
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..554
FT /note="Spir-box"
FT COMPBIAS 488..511
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 442
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..131
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031568"
FT VAR_SEQ 1..48
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11347906"
FT /id="VSP_031569"
FT VAR_SEQ 49..95
FT /note="RGLRGSPGRRLRDTGDLLLRGDGSVGAREPEAAEPATMVVPLASSEA -> M
FT SCLCLGLLWTDSCCLPGRVLGPLHPPAAFSPPHPPAVPPSDRAPVP (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:11347906"
FT /id="VSP_031570"
FT VAR_SEQ 296..297
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031571"
FT VAR_SEQ 594..641
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031572"
FT CONFLICT 41
FT /note="W -> L (in Ref. 1; CAD19439)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="M -> T (in Ref. 4; CAD39070)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="K -> E (in Ref. 2; BAB47461)"
FT /evidence="ECO:0000305"
FT CONFLICT 711
FT /note="L -> F (in Ref. 3; AAI39733)"
FT /evidence="ECO:0000305"
FT HELIX 414..417
FT /evidence="ECO:0007829|PDB:5JCY"
SQ SEQUENCE 714 AA; 79671 MW; 0999F9D5DE6A29CD CRC64;
MARAGSCGGA AAGAGRPEPW ELSLEEVLKA YEQPLNEEQA WAVCFQGCRG LRGSPGRRLR
DTGDLLLRGD GSVGAREPEA AEPATMVVPL ASSEAQTVQS LGFAIYRALD WGLDESEERE
LSPQLERLID LMANNDSEDS GCGAADEGYG GPEEEEEAEG VPRSVRTFAQ AMRLCAARLT
DPRGAQAHYQ AVCRALFVET LELRAFLARV REAKEMLQKL REDEPHLETP RAELDSLGHT
DWARLWVQLM RELRRGVKLK KVQEQEFNPL PTEFQLTPFE MLMQDIRARN YKLRKVMVDG
DIPPRVKKDA HELILDFIRS RPPLKQVSER RLRPLPPKQR SLHEKILEEI KQERRLRPVR
GEGWAARGFG SLPCILNACS GDAKSTSCIN LSVTDAGGSA QRPRPRVLLK APTLAEMEEM
NTSEEEESPC GEVTLKRDRS FSEHDLAQLR SEVASGLQSA THPPGGTEPP RPRAGSAHVW
RPGSRDQGTC PASVSDPSHP LLSNRGSSGD RPEASMTPDA KHLWLEFSHP VESLALTVEE
VMDVRRVLVK AEMEKFLQNK ELFSSLKKGK ICCCCRAKFP LFSWPPSCLF CKRAVCTSCS
IKMKMPSKKF GHIPVYTLGF ESPQRVSAAK TAPIQRRDIF QSLQGPQWQS VEEAFPHIYS
HGCVLKDVCS ECTSFVADVV RSSRKSVDVL NTTPRRSRQT QSLYIPNTRT LDFK
