LOCUS       NP_065875               1958 aa            linear   PRI 27-APR-2025
DEFINITION  rho GTPase-activating protein 21 isoform a [Homo sapiens].
ACCESSION   NP_065875
VERSION     NP_065875.3
DBSOURCE    REFSEQ: accession NM_020824.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 1958)
  AUTHORS   Xie,Z., Liu,L., Fang,J., Zhong,X., Lin,J. and Chen,F.
  TITLE     [ARHGAP21 inhibits epithelial-mesenchymal transition by
            inactivating the WNT signaling pathway in non-small cell lung
            cancer]
  JOURNAL   Nan Fang Yi Ke Da Xue Xue Bao 43 (8), 1322-1332 (2023)
   PUBMED   37712268
  REMARK    GeneRIF: [ARHGAP21 inhibits epithelial-mesenchymal transition by
            inactivating the WNT signaling pathway in non-small cell lung
            cancer].
REFERENCE   2  (residues 1 to 1958)
  AUTHORS   Lazarini,M., Assis-Mendonca,G.R., Machado-Neto,J.A.,
            Latuf-Filho,P., Bezerra,S.M., Vieira,K.P. and Saad,S.T.O.
  TITLE     Silencing of ARHGAP21, a Rho GTPase activating protein (RhoGAP),
            reduces the growth of prostate cancer xenografts in NOD/SCID mice
  JOURNAL   Biochim Biophys Acta Mol Cell Res 1870 (4), 119439 (2023)
   PUBMED   36764390
  REMARK    GeneRIF: Silencing of ARHGAP21, a Rho GTPase activating protein
            (RhoGAP), reduces the growth of prostate cancer xenografts in
            NOD/SCID mice.
REFERENCE   3  (residues 1 to 1958)
  AUTHORS   Segal,D., Maier,S., Mastromarco,G.J., Qian,W.W., Nabeel-Shah,S.,
            Lee,H., Moore,G., Lacoste,J., Larsen,B., Lin,Z.Y.,
            Selvabaskaran,A., Liu,K., Smibert,C., Zhang,Z., Greenblatt,J.,
            Peng,J., Lee,H.O., Gingras,A.C. and Taipale,M.
  TITLE     A central chaperone-like role for 14-3-3 proteins in human cells
  JOURNAL   Mol Cell 83 (6), 974-993 (2023)
   PUBMED   36931259
REFERENCE   4  (residues 1 to 1958)
  AUTHORS   Wang,Z., Wu,S., Wang,G., Yang,Z., Zhang,Y., Zhu,C. and Qin,X.
  TITLE     ARHGAP21 Is Involved in the Carcinogenic Mechanism of
            Cholangiocarcinoma: A Study Based on Bioinformatic Analyses and
            Experimental Validation
  JOURNAL   Medicina (Kaunas) 59 (1), 139 (2023)
   PUBMED   36676763
  REMARK    GeneRIF: ARHGAP21 Is Involved in the Carcinogenic Mechanism of
            Cholangiocarcinoma: A Study Based on Bioinformatic Analyses and
            Experimental Validation.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 1958)
  AUTHORS   Menetrey,J., Perderiset,M., Cicolari,J., Dubois,T., Elkhatib,N., El
            Khadali,F., Franco,M., Chavrier,P. and Houdusse,A.
  TITLE     Structural basis for ARF1-mediated recruitment of ARHGAP21 to Golgi
            membranes
  JOURNAL   EMBO J 26 (7), 1953-1962 (2007)
   PUBMED   17347647
  REMARK    GeneRIF: The crystal structure of the activated GTP-bound form of
            ARF1 in a complex with the Arf-binding domain (ArfBD) of ARHGAP21
            at 2.1 A resolution, is presented.
REFERENCE   6  (residues 1 to 1958)
  AUTHORS   Benzinger,A., Muster,N., Koch,H.B., Yates,J.R. 3rd and Hermeking,H.
  TITLE     Targeted proteomic analysis of 14-3-3 sigma, a p53 effector
            commonly silenced in cancer
  JOURNAL   Mol Cell Proteomics 4 (6), 785-795 (2005)
   PUBMED   15778465
REFERENCE   7  (residues 1 to 1958)
  AUTHORS   Dubois,T., Paleotti,O., Mironov,A.A., Fraisier,V., Stradal,T.E., De
            Matteis,M.A., Franco,M. and Chavrier,P.
  TITLE     Golgi-localized GAP for Cdc42 functions downstream of ARF1 to
            control Arp2/3 complex and F-actin dynamics
  JOURNAL   Nat Cell Biol 7 (4), 353-364 (2005)
   PUBMED   15793564
  REMARK    GeneRIF: The ARHGAP10 protein is a novel Rho GTPase-activating
            protein (Rho-GAP) that is recruited to Golgi membranes through
            binding to GTP-ARF1.
REFERENCE   8  (residues 1 to 1958)
  AUTHORS   Meek,S.E., Lane,W.S. and Piwnica-Worms,H.
  TITLE     Comprehensive proteomic analysis of interphase and mitotic
            14-3-3-binding proteins
  JOURNAL   J Biol Chem 279 (31), 32046-32054 (2004)
   PUBMED   15161933
REFERENCE   9  (residues 1 to 1958)
  AUTHORS   Basseres,D.S., Tizzei,E.V., Duarte,A.A., Costa,F.F. and Saad,S.T.
  TITLE     ARHGAP10, a novel human gene coding for a potentially cytoskeletal
            Rho-GTPase activating protein
  JOURNAL   Biochem Biophys Res Commun 294 (3), 579-585 (2002)
   PUBMED   12056806
  REMARK    GeneRIF: ARHGAP10 gene is highly expressed in muscle and brain,
            which are highly differentiated tissues. It supports the hypothesis
            that ARHGAP10 is important for cell differentiation
REFERENCE   10 (residues 1 to 1958)
  AUTHORS   Robertson,N.G., Khetarpal,U., Gutierrez-Espeleta,G.A., Bieber,F.R.
            and Morton,C.C.
  TITLE     Isolation of novel and known genes from a human fetal cochlear cDNA
            library using subtractive hybridization and differential screening
  JOURNAL   Genomics 23 (1), 42-50 (1994)
   PUBMED   7829101
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AL355979.11, AV709499.1, AF480466.1, AB037845.2, BI491305.1 and
            BQ026288.1.
            
            On Sep 17, 2008 this sequence version replaced NP_065875.2.
            
            Summary: ARHGAP21 functions preferentially as a GTPase-activating
            protein (GAP) for CDC42 (MIM 116952) and regulates the ARP2/3
            complex (MIM 604221) and F-actin dynamics at the Golgi through
            control of CDC42 activity (Dubois et al., 2005 [PubMed
            15793564]).[supplied by OMIM, Mar 2008].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (a). Variants 1, 2, and 3 all encode the same isoform (a).
            
            Sequence Note: The 5'-most in-frame translation start codon is
            selected for this RefSeq and is well-conserved among mammalian
            species. An alternative start codon that would reduce the protein
            length by 1 aa is also present. The use of the downstream start
            codon is assumed in the literature, including PMIDs:12056806,
            15793564 and 17347647.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF480466.1, SRR1803615.86871.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000396432.7/ ENSP00000379709.2
            RefSeq Select criteria :: based on conservation
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..1958
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10p12.1"
     Protein         1..1958
                     /product="rho GTPase-activating protein 21 isoform a"
                     /note="rho GTPase-activating protein 21; Rho-GTPase
                     activating protein 10; rho GTPase-activating protein 10;
                     rho-type GTPase-activating protein 21"
                     /calculated_mol_wt=217332
     Region          1..42
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            36
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q6DFV3; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          48..156
                     /region_name="PDZ_ARHGAP21_23-like"
                     /note="PDZ domain of ARHGAP21 and ARHGAP23, and related
                     domains; cd06756"
                     /db_xref="CDD:467238"
     Site            57
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:20068231; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            order(59..65,105,108,137,141,144..145)
                     /site_type="other"
                     /note="peptide binding site [polypeptide binding]"
                     /db_xref="CDD:467238"
     Region          286..325
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          418..458
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            459
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18669648; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            554
                     /site_type="methylation"
                     /note="Omega-N-methylarginine.
                     /evidence=ECO:0007744|PubMed:24129315; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            575
                     /site_type="methylation"
                     /note="Omega-N-methylarginine.
                     /evidence=ECO:0007744|PubMed:24129315; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            612
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            616
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            625
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          659..751
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            717
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:20068231; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            747
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            857
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:20068231,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          859..885
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            862
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q6DFV3; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            881
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            882
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine.
                     /evidence=ECO:0007744|PubMed:24275569; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            924
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18669648,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            926
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q6DFV3; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          930..1097
                     /region_name="Interaction with ARF1 and ARF6.
                     /evidence=ECO:0000269|PubMed:15793564"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          933..1042
                     /region_name="PH_ARHGAP21-like"
                     /note="ARHGAP21 and related proteins pleckstrin homology
                     (PH) domain; cd01253"
                     /db_xref="CDD:269955"
     Site            order(933..950,955..981,983..1015,1017..1040)
                     /site_type="other"
                     /note="ARF1 binding site [polypeptide binding]"
                     /db_xref="CDD:269955"
     Site            954
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          1086..1133
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            1099
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q6DFV3; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            1115
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          1144..1339
                     /region_name="RhoGAP_ARHGAP21"
                     /note="RhoGAP (GTPase-activator protein [GAP] for Rho-like
                     small GTPases) domain of ArhGAP21-like proteins. ArhGAP21
                     is a multi-domain protein, containing RhoGAP, PH and PDZ
                     domains, and is believed to play a role in the
                     organization of the cell-cell junction...; cd04395"
                     /db_xref="CDD:239860"
     Site            order(1184,1224,1228,1297,1300..1301,1325)
                     /site_type="other"
                     /note="putative GTPase interaction site [polypeptide
                     binding]"
                     /db_xref="CDD:239860"
     Site            1184
                     /site_type="active"
                     /note="catalytic residue [active]"
                     /db_xref="CDD:239860"
     Region          1348..1401
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          1418..1575
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            1418
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            1432
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:20068231,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            1433
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:20068231,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            1504
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            1516
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0007744|PubMed:24275569; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            1527
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:20068231,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          1592..1861
                     /region_name="Interaction with CTNNA1.
                     /evidence=ECO:0000269|PubMed:16184169"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          1598..1642
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          1655..1686
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            1669
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18669648,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            1682
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0000250|UniProtKB:Q6DFV3; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            1742
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Region          1860..1958
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q5T5U3.2)"
     Site            1917
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q6DFV3; propagated from
                     UniProtKB/Swiss-Prot (Q5T5U3.2)"
     CDS             1..1958
                     /gene="ARHGAP21"
                     /gene_synonym="ARHGAP10"
                     /coded_by="NM_020824.4:707..6583"
                     /note="isoform a is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS7144.2"
                     /db_xref="GeneID:57584"
                     /db_xref="HGNC:HGNC:23725"
                     /db_xref="MIM:609870"
ORIGIN      
        1 mmatrrtgls egdgdklkac evsknkdgke qsetvslsed etfswpgpkt vtlkrtsqgf
       61 gftlrhfivy ppesaiqfsy kdeengnrgg kqrnrlepmd tifvkqvkeg gpafeaglct
      121 gdriikvnge svigktysqv ialiqnsdtt lelsvmpkde dilqvlqftk dvtalaysqd
      181 aylkgneays gnarnipepp picypwlpsa psamaqpvei sppdsslskq qtstpvltqp
      241 grayrmeiqv ppsptdvaks ntavcvcnes vrtvivpsek vvdllsnrnn htgpshrtee
      301 vrygvseqts lktvsrttsp plsiptthli hqpagsrsle psgillksgn ysghsdgiss
      361 srsqaveaps vsvnhyspns hqhidwknyk tykeyidnrr lhigcrtiqe rldslraasq
      421 sttdynqvvp nrttlqgrrr stshdrvpqs vqirqrsvsq erledsvlmk ycprsasqga
      481 ltspsvsfsn hrtrswdyie gqdetlenvn sgtpipdsng ekkqtykwsg fteqddrrgi
      541 cerprqqeih ksfrgsnftv apsvvnsdnr rmsgrgvgsv sqfkkippdl ktlqsnrnfq
      601 ttcgmslprg isqdrsplvk vrsnslkaps thvtkpsfsq ksfvsikdqr pvnhlhqnsl
      661 lnqqtwvrtd sapdqqvetg kspslsgasa kpapqssena gtsdlelpvs qrnqdlslqe
      721 aeteqsdtld nkeavilrek ppsgrqtpqp lrhqsyilav ndqetgsdtt cwlpndarre
      781 vhikrmeerk asstsppgds lasipfidep tspsidhdia hipasavisa stsqvpsiat
      841 vppclttsap lirrqlshdh esvgppslda qpnsktersk sydeglddyr edaklsfkhv
      901 sslkgikiad sqkssedsgs rkdsssevfs daakegwlhf rplvtdkgkr vggsirpwkq
      961 myvvlrghsl ylykdkreqt tpseeeqpis vnaclidisy setkrknvfr lttsdceclf
     1021 qaedrddmla wiktiqessn lneedtgvtn rdlisrrike ynnlmskaeq lpktprqsls
     1081 irqtllgaks epktqsphsp keeserklls kddtsppkdk gtwrkgipsi mrktfekkpt
     1141 atgtfgvrld dcppahtnry iplivdicck lveergleyt giyrvpgnna aissmqeeln
     1201 kgmadidiqd dkwrdlnvis sllksffrkl peplftndky adfieanrke dpldrlktlk
     1261 rlihdlpehh yetlkflsah lktvaensek nkmeprnlai vfgptlvrts ednmthmvth
     1321 mpdqykivet liqhhdwfft eegaeepltt vqeestvdsq pvpnidhllt nigrtgvspg
     1381 dvsdsatsds tkskgswgsg kdqysrellv ssifaaasrk rkkpkekaqp sssedeldnv
     1441 ffkkenveqc hndtkeeskk esetlgrkqk iiiakenstr kdpsttkdek islgkestps
     1501 eepspphnsk hnksptlscr failkesprs llaqksshle etgsdsgtll stssqaslar
     1561 fsmkkstspe tkhseflanv stitsdystt ssatyltsld ssrlspevqs vaeskgdead
     1621 derseliseg rpvetdsese fpvfptalts erlfrgklqe vtkssrrnse gselsctegs
     1681 ltssldsrrq lfsshkliec dtlsrkksar fksdsgslgd aknekeapsl tkvfdvmkkg
     1741 kstgslltpt rgesekqept wktkiadrlk lrprapaddm fgvgnhkvna etakrksirr
     1801 rhtlgghrda teisvlnfwk vheqsgeres elsavnrlkp kcsaqdlsis dwlarerlrt
     1861 stsdlsrgei gdpqtenpst reiattdtpl slhcntgsss stlastnrpl lsippqspdq
     1921 ingesfqnvs knassaanaq phklsetpgs kaefhpcl
//
