CAZA1_HUMAN
ID CAZA1_HUMAN Reviewed; 286 AA.
AC P52907; Q53FQ6; Q6FHD5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=F-actin-capping protein subunit alpha-1;
DE AltName: Full=CapZ alpha-1;
GN Name=CAPZA1;
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].
RC TISSUE=Placenta;
RX PubMed=9331217;
RX DOI=10.1002/(sici)1097-0169(1997)38:2<120::aid-cm2>3.0.co;2-b;
RA Hart M.C., Korshunova Y.O., Cooper J.A.;
RT "Vertebrates have conserved capping protein alpha isoforms with specific
RT expression patterns.";
RL Cell Motil. Cytoskeleton 38:120-132(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Gastric mucosa;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix;
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 [7]
RP PROTEIN SEQUENCE OF 2-12 AND 178-192, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=T-cell;
RA Bienvenut W.V., Kanor S., Tissot J.-D., Quadroni M.;
RL Submitted (MAY-2006) to UniProtKB.
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP IDENTIFICATION IN THE WASH COMPLEX.
RX PubMed=19922875; DOI=10.1016/j.devcel.2009.09.010;
RA Derivery E., Sousa C., Gautier J.J., Lombard B., Loew D., Gautreau A.;
RT "The Arp2/3 activator WASH controls the fission of endosomes through a
RT large multiprotein complex.";
RL Dev. Cell 17:712-723(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-19 AND LYS-97, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP FUNCTION, AND INTERACTION WITH CD2AP AND SH3BP1.
RX PubMed=22891260; DOI=10.1083/jcb.201202094;
RA Elbediwy A., Zihni C., Terry S.J., Clark P., Matter K., Balda M.S.;
RT "Epithelial junction formation requires confinement of Cdc42 activity by a
RT novel SH3BP1 complex.";
RL J. Cell Biol. 198:677-693(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND IDENTIFICATION BY MASS
RP 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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [16]
RP INTERACTION WITH CRACD.
RX PubMed=30361697; DOI=10.1038/s41556-018-0215-z;
RA Jung Y.S., Wang W., Jun S., Zhang J., Srivastava M., Kim M.J., Lien E.M.,
RA Shang J., Chen J., McCrea P.D., Zhang S., Park J.I.;
RT "Deregulation of CRAD-controlled cytoskeleton initiates mucinous colorectal
RT cancer via beta-catenin.";
RL Nat. Cell Biol. 20:1303-1314(2018).
RN [17]
RP VARIANT LEU-219.
RX PubMed=24951542; DOI=10.1093/hmg/ddu318;
RA Khan M.A., Rupp V.M., Orpinell M., Hussain M.S., Altmueller J.,
RA Steinmetz M.O., Enzinger C., Thiele H., Hoehne W., Nuernberg G., Baig S.M.,
RA Ansar M., Nuernberg P., Vincent J.B., Speicher M.R., Goenczy P.,
RA Windpassinger C.;
RT "A missense mutation in the PISA domain of HsSAS-6 causes autosomal
RT recessive primary microcephaly in a large consanguineous Pakistani
RT family.";
RL Hum. Mol. Genet. 23:5940-5949(2014).
RN [18]
RP STRUCTURE BY NMR OF 265-276 IN COMPLEX WITH S100B AND CALCIUM.
RX PubMed=12470955; DOI=10.1016/s0022-2836(02)01152-x;
RA Inman K.G., Yang R., Rustandi R.R., Miller K.E., Baldisseri D.M.,
RA Weber D.J.;
RT "Solution NMR structure of S100B bound to the high-affinity target peptide
RT TRTK-12.";
RL J. Mol. Biol. 324:1003-1014(2002).
RN [19]
RP STRUCTURE BY NMR OF 265-276 IN COMPLEX WITH S100B AND CALCIUM.
RX PubMed=12480931; DOI=10.1074/jbc.m210622200;
RA McClintock K.A., Shaw G.S.;
RT "A novel S100 target conformation is revealed by the solution structure of
RT the Ca2+-S100B-TRTK-12 complex.";
RL J. Biol. Chem. 278:6251-6257(2003).
CC -!- FUNCTION: F-actin-capping proteins bind in a Ca(2+)-independent manner
CC to the fast growing ends of actin filaments (barbed end) thereby
CC blocking the exchange of subunits at these ends. Unlike other capping
CC proteins (such as gelsolin and severin), these proteins do not sever
CC actin filaments. May play a role in the formation of epithelial cell
CC junctions. {ECO:0000269|PubMed:22891260}.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. Interacts with
CC S100A (By similarity). Component of the WASH complex, composed of F-
CC actin-capping protein subunit alpha (CAPZA1, CAPZA2 or CAPZA3), F-
CC actin-capping protein subunit beta (CAPZB), WASH (WASHC1, WASH2P,
CC WASH3P, WASH4P, WASH5P or WASH6P), WASHC2 (WASHC2A or WASHC2C), WASHC3,
CC WASHC4 and WASHC5. Interacts with S100B. Interacts with SH3BP1;
CC recruits CAPZA1 to forming cell junctions (PubMed:22891260). Interacts
CC with CD2AP (PubMed:22891260). Directly interacts with CRACD; this
CC interaction decreases binding to actin (PubMed:30361697). {ECO:0000250,
CC ECO:0000269|PubMed:12470955, ECO:0000269|PubMed:12480931,
CC ECO:0000269|PubMed:19922875, ECO:0000269|PubMed:22891260,
CC ECO:0000269|PubMed:30361697}.
CC -!- INTERACTION:
CC P52907; P23297: S100A1; NbExp=2; IntAct=EBI-355586, EBI-743686;
CC P52907; P33763: S100A5; NbExp=2; IntAct=EBI-355586, EBI-7211732;
CC P52907; P04271: S100B; NbExp=3; IntAct=EBI-355586, EBI-458391;
CC P52907; P25815: S100P; NbExp=2; IntAct=EBI-355586, EBI-743700;
CC P52907; Q96B97: SH3KBP1; NbExp=5; IntAct=EBI-355586, EBI-346595;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the F-actin-capping protein alpha subunit
CC family. {ECO:0000305}.
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DR EMBL; U56637; AAC00533.1; -; mRNA.
DR EMBL; CR407657; CAG28585.1; -; mRNA.
DR EMBL; CR541819; CAG46618.1; -; mRNA.
DR EMBL; BT019364; AAV38171.1; -; mRNA.
DR EMBL; AK223226; BAD96946.1; -; mRNA.
DR EMBL; AL603832; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL929470; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000144; AAH00144.1; -; mRNA.
DR CCDS; CCDS30805.1; -.
DR PIR; G02639; G02639.
DR RefSeq; NP_006126.1; NM_006135.2.
DR PDB; 1MQ1; NMR; -; C/D=265-276.
DR PDB; 1MWN; NMR; -; X/Y=265-276.
DR PDBsum; 1MQ1; -.
DR PDBsum; 1MWN; -.
DR AlphaFoldDB; P52907; -.
DR SMR; P52907; -.
DR BioGRID; 107279; 238.
DR CORUM; P52907; -.
DR IntAct; P52907; 109.
DR MINT; P52907; -.
DR STRING; 9606.ENSP00000263168; -.
DR ChEMBL; CHEMBL4295781; -.
DR GlyGen; P52907; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P52907; -.
DR MetOSite; P52907; -.
DR PhosphoSitePlus; P52907; -.
DR SwissPalm; P52907; -.
DR BioMuta; CAPZA1; -.
DR OGP; P52907; -.
DR REPRODUCTION-2DPAGE; IPI00005969; -.
DR REPRODUCTION-2DPAGE; P52907; -.
DR SWISS-2DPAGE; P52907; -.
DR EPD; P52907; -.
DR jPOST; P52907; -.
DR MassIVE; P52907; -.
DR MaxQB; P52907; -.
DR PaxDb; P52907; -.
DR PeptideAtlas; P52907; -.
DR PRIDE; P52907; -.
DR ProteomicsDB; 56550; -.
DR TopDownProteomics; P52907; -.
DR Antibodypedia; 33824; 315 antibodies from 30 providers.
DR DNASU; 829; -.
DR Ensembl; ENST00000263168.4; ENSP00000263168.3; ENSG00000116489.13.
DR GeneID; 829; -.
DR KEGG; hsa:829; -.
DR MANE-Select; ENST00000263168.4; ENSP00000263168.3; NM_006135.3; NP_006126.1.
DR UCSC; uc001ecj.2; human.
DR CTD; 829; -.
DR DisGeNET; 829; -.
DR GeneCards; CAPZA1; -.
DR HGNC; HGNC:1488; CAPZA1.
DR HPA; ENSG00000116489; Low tissue specificity.
DR MIM; 601580; gene.
DR neXtProt; NX_P52907; -.
DR OpenTargets; ENSG00000116489; -.
DR PharmGKB; PA26069; -.
DR VEuPathDB; HostDB:ENSG00000116489; -.
DR eggNOG; KOG0836; Eukaryota.
DR GeneTree; ENSGT00950000183119; -.
DR HOGENOM; CLU_045161_0_0_1; -.
DR InParanoid; P52907; -.
DR OMA; LKVDVHY; -.
DR OrthoDB; 1200844at2759; -.
DR PhylomeDB; P52907; -.
DR TreeFam; TF314822; -.
DR PathwayCommons; P52907; -.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-HSA-6807878; COPI-mediated anterograde transport.
DR Reactome; R-HSA-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR Reactome; R-HSA-879415; Advanced glycosylation endproduct receptor signaling.
DR Reactome; R-HSA-8950505; Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation.
DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; P52907; -.
DR SIGNOR; P52907; -.
DR BioGRID-ORCS; 829; 18 hits in 1079 CRISPR screens.
DR ChiTaRS; CAPZA1; human.
DR EvolutionaryTrace; P52907; -.
DR GenomeRNAi; 829; -.
DR Pharos; P52907; Tbio.
DR PRO; PR:P52907; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P52907; protein.
DR Bgee; ENSG00000116489; Expressed in epithelium of nasopharynx and 213 other tissues.
DR Genevisible; P52907; HS.
DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0008290; C:F-actin capping protein complex; IBA:GO_Central.
DR GO; GO:0071203; C:WASH complex; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; TAS:ProtInc.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0051016; P:barbed-end actin filament capping; IBA:GO_Central.
DR GO; GO:0034329; P:cell junction assembly; IMP:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR Gene3D; 3.30.1140.60; -; 1.
DR Gene3D; 3.90.1150.210; -; 1.
DR IDEAL; IID00122; -.
DR InterPro; IPR002189; CapZ_alpha.
DR InterPro; IPR037282; CapZ_alpha/beta.
DR InterPro; IPR042276; CapZ_alpha/beta_2.
DR InterPro; IPR042489; CapZ_alpha_1.
DR InterPro; IPR017865; F-actin_cap_asu_CS.
DR PANTHER; PTHR10653; PTHR10653; 1.
DR Pfam; PF01267; F-actin_cap_A; 1.
DR PRINTS; PR00191; FACTINCAPA.
DR SUPFAM; SSF90096; SSF90096; 1.
DR PROSITE; PS00748; F_ACTIN_CAPPING_A_1; 1.
DR PROSITE; PS00749; F_ACTIN_CAPPING_A_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin capping; Actin-binding; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Phosphoprotein;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:19413330"
FT CHAIN 2..286
FT /note="F-actin-capping protein subunit alpha-1"
FT /id="PRO_0000208624"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:19413330"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 19
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 97
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VARIANT 219
FT /note="S -> L (in dbSNP:rs555597264)"
FT /evidence="ECO:0000269|PubMed:24951542"
FT /id="VAR_073834"
FT CONFLICT 192
FT /note="L -> P (in Ref. 4; BAD96946)"
FT /evidence="ECO:0000305"
FT HELIX 271..275
FT /evidence="ECO:0007829|PDB:1MWN"
SQ SEQUENCE 286 AA; 32923 MW; 0F47ADAB6A3689DD CRC64;
MADFDDRVSD EEKVRIAAKF ITHAPPGEFN EVFNDVRLLL NNDNLLREGA AHAFAQYNMD
QFTPVKIEGY EDQVLITEHG DLGNSRFLDP RNKISFKFDH LRKEASDPQP EEADGGLKSW
RESCDSALRA YVKDHYSNGF CTVYAKTIDG QQTIIACIES HQFQPKNFWN GRWRSEWKFT
ITPPTAQVVG VLKIQVHYYE DGNVQLVSHK DVQDSLTVSN EAQTAKEFIK IIENAENEYQ
TAISENYQTM SDTTFKALRR QLPVTRTKID WNKILSYKIG KEMQNA
