ID AN13A_HUMAN Reviewed; 590 AA.
AC Q8IZ07; O60736;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 3.
DT 27-MAR-2024, entry version 172.
DE RecName: Full=Ankyrin repeat domain-containing protein 13A;
DE AltName: Full=Protein KE03;
GN Name=ANKRD13A; Synonyms=ANKRD13;
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 [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-353.
RC TISSUE=Blood;
RA Zhao Z., Huang X., Li N., Zhu X., Cao X.;
RT "A novel gene from human dendritic cells.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP FUNCTION, INTERACTION WITH EGFR, UBIQUITINATION, UIM DOMAIN,
RP UBIQUITIN-BINDING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 491-ALA--SER-495; 527-ALA--SER-531; 557-ALA--SER-561 AND 582-VAL--SER-586.
RX PubMed=22298428; DOI=10.1091/mbc.e11-09-0817;
RA Tanno H., Yamaguchi T., Goto E., Ishido S., Komada M.;
RT "The Ankrd 13 family of UIM-bearing proteins regulates EGF receptor
RT endocytosis from the plasma membrane.";
RL Mol. Biol. Cell 23:1343-1353(2012).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-586, AND IDENTIFICATION BY
RP 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).
CC -!- FUNCTION: Ubiquitin-binding protein that specifically recognizes and
CC binds 'Lys-63'-linked ubiquitin. Does not bind 'Lys-48'-linked
CC ubiquitin. Positively regulates the internalization of ligand-activated
CC EGFR by binding to the Ub moiety of ubiquitinated EGFR at the cell
CC membrane. {ECO:0000269|PubMed:22298428}.
CC -!- SUBUNIT: Interacts (via the UIM 3 and 4 repeats) with EGFR
CC (ubiquitinated); the interaction is direct, inhibited by ANKRD13A
CC monoubiquitination and may regulate EGFR internalization.
CC {ECO:0000269|PubMed:22298428}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22298428}. Late
CC endosome {ECO:0000269|PubMed:22298428}. Note=Interaction with EGFR may
CC enhance association with the cell membrane.
CC -!- DOMAIN: The UIM repeats 3 and 4 are required for binding to
CC ubiquitinated EGFR and 'Lys-63'-linked ubiquitin.
CC -!- PTM: Monoubiquitinated, inhibits interaction with ubiquitinated EGFR.
CC {ECO:0000269|PubMed:22298428}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC17109.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; BC032833; AAH32833.2; -; mRNA.
DR EMBL; AF064604; AAC17109.1; ALT_FRAME; mRNA.
DR CCDS; CCDS9140.1; -.
DR RefSeq; NP_149112.1; NM_033121.1.
DR AlphaFoldDB; Q8IZ07; -.
DR SMR; Q8IZ07; -.
DR BioGRID; 124582; 161.
DR IntAct; Q8IZ07; 35.
DR MINT; Q8IZ07; -.
DR STRING; 9606.ENSP00000261739; -.
DR iPTMnet; Q8IZ07; -.
DR MetOSite; Q8IZ07; -.
DR PhosphoSitePlus; Q8IZ07; -.
DR BioMuta; ANKRD13A; -.
DR DMDM; 145559439; -.
DR EPD; Q8IZ07; -.
DR jPOST; Q8IZ07; -.
DR MassIVE; Q8IZ07; -.
DR MaxQB; Q8IZ07; -.
DR PaxDb; 9606-ENSP00000261739; -.
DR PeptideAtlas; Q8IZ07; -.
DR ProteomicsDB; 71265; -.
DR Pumba; Q8IZ07; -.
DR Antibodypedia; 49620; 107 antibodies from 18 providers.
DR DNASU; 88455; -.
DR Ensembl; ENST00000261739.9; ENSP00000261739.4; ENSG00000076513.17.
DR GeneID; 88455; -.
DR KEGG; hsa:88455; -.
DR MANE-Select; ENST00000261739.9; ENSP00000261739.4; NM_033121.2; NP_149112.1.
DR UCSC; uc001tpx.4; human.
DR AGR; HGNC:21268; -.
DR CTD; 88455; -.
DR DisGeNET; 88455; -.
DR GeneCards; ANKRD13A; -.
DR HGNC; HGNC:21268; ANKRD13A.
DR HPA; ENSG00000076513; Low tissue specificity.
DR MIM; 615123; gene.
DR neXtProt; NX_Q8IZ07; -.
DR OpenTargets; ENSG00000076513; -.
DR PharmGKB; PA134884324; -.
DR VEuPathDB; HostDB:ENSG00000076513; -.
DR eggNOG; KOG0522; Eukaryota.
DR GeneTree; ENSGT00950000182928; -.
DR HOGENOM; CLU_026137_2_0_1; -.
DR InParanoid; Q8IZ07; -.
DR OMA; INQTHAY; -.
DR OrthoDB; 20116at2759; -.
DR PhylomeDB; Q8IZ07; -.
DR TreeFam; TF314176; -.
DR PathwayCommons; Q8IZ07; -.
DR SignaLink; Q8IZ07; -.
DR SIGNOR; Q8IZ07; -.
DR BioGRID-ORCS; 88455; 7 hits in 1151 CRISPR screens.
DR ChiTaRS; ANKRD13A; human.
DR GenomeRNAi; 88455; -.
DR Pharos; Q8IZ07; Tbio.
DR PRO; PR:Q8IZ07; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8IZ07; Protein.
DR Bgee; ENSG00000076513; Expressed in upper arm skin and 191 other cell types or tissues.
DR ExpressionAtlas; Q8IZ07; baseline and differential.
DR Genevisible; Q8IZ07; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0140036; F:ubiquitin-dependent protein binding; IDA:UniProtKB.
DR GO; GO:1905667; P:negative regulation of protein localization to endosome; IDA:UniProtKB.
DR GO; GO:0002091; P:negative regulation of receptor internalization; IMP:UniProtKB.
DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1.
DR InterPro; IPR021832; ANKRD13.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR003903; UIM_dom.
DR PANTHER; PTHR12447; ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 13; 1.
DR PANTHER; PTHR12447:SF4; ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 13A; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF11904; GPCR_chapero_1; 1.
DR SMART; SM00248; ANK; 2.
DR SMART; SM00726; UIM; 3.
DR SUPFAM; SSF48403; Ankyrin repeat; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
DR PROSITE; PS50330; UIM; 3.
PE 1: Evidence at protein level;
KW ANK repeat; Cell membrane; Endosome; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..590
FT /note="Ankyrin repeat domain-containing protein 13A"
FT /id="PRO_0000066909"
FT REPEAT 40..69
FT /note="ANK 1"
FT REPEAT 73..102
FT /note="ANK 2"
FT DOMAIN 483..502
FT /note="UIM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 519..538
FT /note="UIM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 549..568
FT /note="UIM 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 574..590
FT /note="UIM 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT MOD_RES 205
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80UP5"
FT MOD_RES 586
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 505
FT /note="L -> P (in dbSNP:rs2287174)"
FT /id="VAR_048276"
FT MUTAGEN 491..495
FT /note="AIQQS->GIQQA: No effect on 'Lys-63'-linked ubiquitin
FT binding and interaction with EGFR. No effect on 'Lys-63'-
FT linked ubiquitin binding and interaction with EGFR; when
FT associated with 527-G--A-531. Inhibits 'Lys-63'-linked
FT ubiquitin binding; when associated with 527-G--A-531 and
FT 557-G--A-561. Abolishes 'Lys-63'-linked ubiquitin binding
FT and interaction with EGFR; when associated with 527-G--A-
FT 531, 557-G--A-561 and 582-G--A-586."
FT /evidence="ECO:0000269|PubMed:22298428"
FT MUTAGEN 527..531
FT /note="AIQES->GIQEA: No effect on 'Lys-63'-linked ubiquitin
FT binding and interaction with EGFR. No effect on 'Lys-63'-
FT linked ubiquitin binding and interaction with EGFR; when
FT associated with 491-G--A-495. Inhibits 'Lys-63'-linked
FT ubiquitin binding; when associated with 557-G--A-561.
FT Inhibits 'Lys-63'-linked ubiquitin binding; when associated
FT with 491-G--A-495 and 557-G--A-561. Strongly inhibits 'Lys-
FT 63'-linked ubiquitin binding; when associated with 557-G--
FT A-561 and 582-G--A-586. Abolishes 'Lys-63'-linked ubiquitin
FT binding and interaction with EGFR; when associated with
FT 491-G--A-495, 557-G--A-561 and 582-G--A-586."
FT /evidence="ECO:0000269|PubMed:22298428"
FT MUTAGEN 557..561
FT /note="AMELS->GMELA: Slightly inhibits 'Lys-63'-linked
FT ubiquitin binding and strongly inhibits interaction with
FT EGFR. No effect on 'Lys-63'-linked ubiquitin binding and
FT interaction with EGFR; when associated with 527-G--A-531.
FT Inhibits 'Lys-63'-linked ubiquitin binding and interaction
FT with EGFR; when associated with 491-G--A-495 and 527-G--A-
FT 531. Abolishes 'Lys-63'-linked ubiquitin binding and
FT interaction with EGFR; when associated with 582-V--S-586.
FT Abolishes 'Lys-63'-linked ubiquitin binding and interaction
FT with EGFR; when associated with 491-G--A-495, 527-G--A-531
FT and 582-G--A-586."
FT /evidence="ECO:0000269|PubMed:22298428"
FT MUTAGEN 582..586
FT /note="VLQLS->GLQLA: Abolishes 'Lys-63'-linked ubiquitin
FT binding and strongly inhibits interaction with EGFR.
FT Abolishes 'Lys-63'-linked ubiquitin binding and interaction
FT with EGFR; when associated with 557-G--A-561. Strongly
FT inhibits 'Lys-63'-linked ubiquitin binding; when associated
FT with 527-G--A-531 and 557-G--A-561. Abolishes 'Lys-63'-
FT linked ubiquitin binding and interaction with EGFR; when
FT associated with 491-G--A-495, 527-G--A-531 and 557-G--A-
FT 561."
FT /evidence="ECO:0000269|PubMed:22298428"
FT CONFLICT 193
FT /note="D -> G (in Ref. 2; AAC17109)"
FT /evidence="ECO:0000305"
FT CONFLICT 296
FT /note="D -> G (in Ref. 1; AAH32833)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 590 AA; 67619 MW; 25D0B712D1A1B0B9 CRC64;
MSSACDAGDH YPLHLLVWKN DYRQLEKELQ GQNVEAVDPR GRTLLHLAVS LGHLESARVL
LRHKADVTKE NRQGWTVLHE AVSTGDPEMV YTVLQHRDYH NTSMALEGVP ELLQKILEAP
DFYVQMKWEF TSWVPLVSRI CPNDVCRIWK SGAKLRVDIT LLGFENMSWI RGRRSFIFKG
EDNWAELMEV NHDDKVVTTE RFDLSQEMER LTLDLMKPKS REVERRLTSP VINTSLDTKN
IAFERTKSGF WGWRTDKAEV VNGYEAKVYT VNNVNVITKI RTEHLTEEEK KRYKADRNPL
ESLLGTVEHQ FGAQGDLTTE CATANNPTAI TPDEYFNEEF DLKDRDIGRP KELTIRTQKF
KAMLWMCEEF PLSLVEQVIP IIDLMARTSA HFARLRDFIK LEFPPGFPVK IEIPLFHVLN
ARITFGNVNG CSTAEESVSQ NVEGTQADSA SHITNFEVDQ SVFEIPESYY VQDNGRNVHL
QDEDYEIMQF AIQQSLLESS RSQELSGPAS NGGISQTNTY DAQYERAIQE SLLTSTEGLC
PSALSETSRF DNDLQLAMEL SAKELEEWEL RLQEEEAELQ QVLQLSLTDK
//
