RBCC

ANKRD13A (ANKRD13) [Confidence: low (only semi-automatic identification from reviews)]
Ankyrin repeat domain-containing protein 13A (Protein KE03)

UniProt Q8IZ07
ID AN13A_HUMAN Reviewed; 590 AA.
AC Q8IZ07; O60736;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-APR-2007, sequence version 3.
DT 22-JAN-2014, entry version 96.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT project: 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.,
RA Buerckstuemmer T., 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
RP 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).
CC -!- FUNCTION: Ubiquitin-binding protein that specifically recognizes
CC and binds 'Lys-63'-linked ubiquitin. Does not bind 'Lys-48'-linked
CC ubiquitin. Positively regulates the internalization of ligand-
CC activated EGFR by binding to the Ub moiety of ubiquitinated EGFR
CC at the cell membrane.
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 -!- SUBCELLULAR LOCATION: Cell membrane. Late endosome.
CC Note=Interaction with EGFR may enhance association with the cell
CC 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
CC EGFR.
CC -!- SIMILARITY: Contains 2 ANK repeats.
CC -!- SIMILARITY: Contains 4 UIM (ubiquitin-interacting motif) repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC17109.1; Type=Frameshift; Positions=343, 348;
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DR EMBL; BC032833; AAH32833.2; -; mRNA.
DR EMBL; AF064604; AAC17109.1; ALT_FRAME; mRNA.
DR RefSeq; NP_149112.1; NM_033121.1.
DR UniGene; Hs.528703; -.
DR ProteinModelPortal; Q8IZ07; -.
DR SMR; Q8IZ07; 3-96.
DR IntAct; Q8IZ07; 6.
DR MINT; MINT-1191854; -.
DR STRING; 9606.ENSP00000261739; -.
DR PhosphoSite; Q8IZ07; -.
DR DMDM; 145559439; -.
DR PaxDb; Q8IZ07; -.
DR PRIDE; Q8IZ07; -.
DR DNASU; 88455; -.
DR Ensembl; ENST00000261739; ENSP00000261739; ENSG00000076513.
DR GeneID; 88455; -.
DR KEGG; hsa:88455; -.
DR UCSC; uc001tpx.3; human.
DR CTD; 88455; -.
DR GeneCards; GC12P110437; -.
DR HGNC; HGNC:21268; ANKRD13A.
DR HPA; HPA039488; -.
DR MIM; 615123; gene.
DR neXtProt; NX_Q8IZ07; -.
DR PharmGKB; PA134884324; -.
DR eggNOG; NOG304537; -.
DR HOGENOM; HOG000230821; -.
DR HOVERGEN; HBG059287; -.
DR InParanoid; Q8IZ07; -.
DR OMA; EVNHDDR; -.
DR OrthoDB; EOG76QFGX; -.
DR PhylomeDB; Q8IZ07; -.
DR ChiTaRS; ANKRD13A; human.
DR GenomeRNAi; 88455; -.
DR NextBio; 76216; -.
DR PRO; PR:Q8IZ07; -.
DR ArrayExpress; Q8IZ07; -.
DR Bgee; Q8IZ07; -.
DR CleanEx; HS_ANKRD13A; -.
DR Genevestigator; Q8IZ07; -.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR021832; ANKRD13.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR InterPro; IPR003903; Ubiquitin-int_motif.
DR PANTHER; PTHR12447; PTHR12447; 1.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF11904; GPCR_chapero_1; 1.
DR SMART; SM00248; ANK; 2.
DR SMART; SM00726; UIM; 3.
DR SUPFAM; SSF48403; SSF48403; 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; Complete proteome; Endosome; Membrane;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW Ubl conjugation.
FT CHAIN 1 590 Ankyrin repeat domain-containing protein
FT 13A.
FT /FTId=PRO_0000066909.
FT REPEAT 40 69 ANK 1.
FT REPEAT 73 102 ANK 2.
FT REPEAT 483 502 UIM 1.
FT REPEAT 519 538 UIM 2.
FT REPEAT 549 568 UIM 3.
FT REPEAT 574 590 UIM 4.
FT MOD_RES 205 205 Phosphoserine (By similarity).
FT VARIANT 505 505 L -> P (in dbSNP:rs2287174).
FT /FTId=VAR_048276.
FT MUTAGEN 491 495 AIQQS->GIQQA: No effect on 'Lys-63'-
FT linked ubiquitin binding and interaction
FT with EGFR. No effect on 'Lys-63'-linked
FT ubiquitin binding and interaction with
FT EGFR; when associated with 527-G--A-531.
FT Inhibits 'Lys-63'-linked ubiquitin
FT binding; when associated with 527-G--A-
FT 531 and 557-G--A-561. Abolishes 'Lys-63'-
FT linked ubiquitin binding and interaction
FT with EGFR; when associated with 527-G--A-
FT 531, 557-G--A-561 and 582-G--A-586.
FT MUTAGEN 527 531 AIQES->GIQEA: No effect on 'Lys-63'-
FT linked ubiquitin binding and interaction
FT with EGFR. No effect on 'Lys-63'-linked
FT ubiquitin binding and interaction with
FT EGFR; when associated with 491-G--A-495.
FT Inhibits 'Lys-63'-linked ubiquitin
FT binding; when associated with 557-G--A-
FT 561. Inhibits 'Lys-63'-linked ubiquitin
FT binding; when associated with 491-G--A-
FT 495 and 557-G--A-561. Strongly inhibits
FT 'Lys-63'-linked ubiquitin binding; when
FT associated with 557-G--A-561 and 582-G--
FT A-586. Abolishes 'Lys-63'-linked
FT ubiquitin binding and interaction with
FT EGFR; when associated with 491-G--A-495,
FT 557-G--A-561 and 582-G--A-586.
FT MUTAGEN 557 561 AMELS->GMELA: Slightly inhibits 'Lys-63'-
FT linked ubiquitin binding and strongly
FT inhibits interaction with EGFR. No effect
FT on 'Lys-63'-linked ubiquitin binding and
FT interaction with EGFR; when associated
FT with 527-G--A-531. Inhibits 'Lys-63'-
FT linked ubiquitin binding and interaction
FT with EGFR; when associated with 491-G--A-
FT 495 and 527-G--A-531. Abolishes 'Lys-63'-
FT linked ubiquitin binding and interaction
FT with EGFR; when associated with 582-V--S-
FT 586. Abolishes 'Lys-63'-linked ubiquitin
FT binding and interaction with EGFR; when
FT associated with 491-G--A-495, 527-G--A-
FT 531 and 582-G--A-586.
FT MUTAGEN 582 586 VLQLS->GLQLA: Abolishes 'Lys-63'-linked
FT ubiquitin binding and strongly inhibits
FT interaction with EGFR. Abolishes 'Lys-
FT 63'-linked ubiquitin binding and
FT interaction with EGFR; when associated
FT with 557-G--A-561. Strongly inhibits
FT 'Lys-63'-linked ubiquitin binding; when
FT associated with 527-G--A-531 and 557-G--
FT A-561. Abolishes 'Lys-63'-linked
FT ubiquitin binding and interaction with
FT EGFR; when associated with 491-G--A-495,
FT 527-G--A-531 and 557-G--A-561.
FT CONFLICT 193 193 D -> G (in Ref. 2; AAC17109).
FT CONFLICT 296 296 D -> G (in Ref. 1; AAH32833).
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
//

MIM 615123
*RECORD*
*FIELD* NO
615123
*FIELD* TI
*615123 ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 13A; ANKRD13A
*FIELD* TX

DESCRIPTION
read more
Some members of the ANKRD13 family, such as ANKRD13A, have a role in
regulating internalization of cell surface proteins (Tanno et al.,
2012).

CLONING

Tanno et al. (2012) cloned ANKRD13A from a human brain cDNA library. The
deduced 590-amino acid protein contains 3 N-terminal ankyrin repeats and
4 putative C-terminal ubiquitin-interacting motifs. Immunofluorescence
analysis of HeLa cells revealed that ANKRD13A localized to the plasma
membrane and late endosomes.

GENE FUNCTION

Monoubiquitination and/or lys63-linked polyubiquitin chains serve as
endocytosis signals that are tagged to a variety of cell surface
integral membrane proteins. Proteins of the endocytic machinery are also
regulated by their own ubiquitination. Using immunoprecipitation and
Western blot analysis of EGF (131530)-stimulated HeLa cells, Tanno et
al. (2012) showed that ANKRD13A, ANKRD13B (615124), and ANKRD13D
(615126), but not ANKRD13C (615125), bound to the ubiquitinated EGF
receptor (EGFR; 131550). Tanno et al. (2012) found that ANKRD13A was
itself monoubiquitinated, and this ubiquitination interfered with
interaction between ANKRD13A and ubiquitinated EGFR. Both ubiquitination
of ANKRD13A and binding of ANKRD13A to EGFR required the
ubiquitin-interacting motifs of ANKRD13A. Protein binding assays
revealed that ANKRD13A, ANKRD13B, and ANKRD13D bound to lys63-linked,
but not lys48-linked, polyubiquitin chains. Binding affinity was higher
with ubiquitin chain lengths between 4 and 7 units, with lower or no
affinity for shorter ubiquitin chain lengths. Overexpression of
ANKRD13A, ANKRD13B, and ANKRD13B delayed, but did not completely
inhibit, ligand-induced EGFR internalization. ANKRD13 proteins had no
effect on EGFR degradation. Overexpression of ANKRD13A also suppressed
uptake of nonubiquitinated cargo, such as transferrin receptor (TFRC;
190010).

MAPPING

Hartz (2013) mapped the ANKRD13A gene to chromosome 12q24.11 based on an
alignment of the ANKRD13A sequence (GenBank GENBANK AF064604) with the
genomic sequence (GRCh37).

*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 3/5/2013.

2. Tanno, H.; Yamaguchi, T.; Goto, E.; Ishido, S.; Komada, M.: The
Ankrd 13 family of UIM-bearing proteins regulates EGF receptor endocytosis
from the plasma membrane. Molec. Biol. Cell 23: 1343-1353, 2012.

*FIELD* CD
Patricia A. Hartz: 3/19/2013

*FIELD* ED
mgross: 03/19/2013

RBCC Red Blood Cell Collection

Full text data of ANKRD13A