DEN2A_HUMAN
ID DEN2A_HUMAN Reviewed; 1009 AA.
AC Q9ULE3; C9JUI3; Q1RMD5; Q86XY0;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 4.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=DENN domain-containing protein 2A;
GN Name=DENND2A; Synonyms=KIAA1277;
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] (ISOFORM 1), AND VARIANT HIS-156.
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 372-1009 (ISOFORM 1), AND VARIANT HIS-156.
RC TISSUE=Embryonic stem cell, and Liver;
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 FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20937701; DOI=10.1083/jcb.201008051;
RA Yoshimura S., Gerondopoulos A., Linford A., Rigden D.J., Barr F.A.;
RT "Family-wide characterization of the DENN domain Rab GDP-GTP exchange
RT factors.";
RL J. Cell Biol. 191:367-381(2010).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) which may activate
CC RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting
CC inactive GDP-bound Rab proteins into their active GTP-bound form. May
CC play a role in late endosomes back to trans-Golgi network/TGN
CC transport. {ECO:0000269|PubMed:20937701}.
CC -!- INTERACTION:
CC Q9ULE3-2; Q96B97: SH3KBP1; NbExp=3; IntAct=EBI-13305669, EBI-346595;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:20937701}. Note=Associated with actin filaments.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9ULE3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9ULE3-2; Sequence=VSP_019466, VSP_019467;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86591.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB033103; BAA86591.2; ALT_INIT; mRNA.
DR EMBL; AC006452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC069335; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC049193; AAH49193.1; -; mRNA.
DR EMBL; BC115004; AAI15005.1; -; mRNA.
DR CCDS; CCDS43659.1; -. [Q9ULE3-1]
DR CCDS; CCDS83233.1; -. [Q9ULE3-2]
DR RefSeq; NP_001304981.1; NM_001318052.1. [Q9ULE3-1]
DR RefSeq; NP_001304982.1; NM_001318053.1. [Q9ULE3-2]
DR RefSeq; NP_056504.3; NM_015689.4. [Q9ULE3-1]
DR RefSeq; XP_005250034.1; XM_005249977.3.
DR RefSeq; XP_011514354.1; XM_011516052.2.
DR RefSeq; XP_011514355.1; XM_011516053.2. [Q9ULE3-1]
DR RefSeq; XP_016867478.1; XM_017011989.1. [Q9ULE3-1]
DR AlphaFoldDB; Q9ULE3; -.
DR SMR; Q9ULE3; -.
DR BioGRID; 118031; 4.
DR IntAct; Q9ULE3; 4.
DR MINT; Q9ULE3; -.
DR STRING; 9606.ENSP00000275884; -.
DR iPTMnet; Q9ULE3; -.
DR PhosphoSitePlus; Q9ULE3; -.
DR SwissPalm; Q9ULE3; -.
DR BioMuta; DENND2A; -.
DR DMDM; 296439469; -.
DR jPOST; Q9ULE3; -.
DR MassIVE; Q9ULE3; -.
DR MaxQB; Q9ULE3; -.
DR PaxDb; Q9ULE3; -.
DR PeptideAtlas; Q9ULE3; -.
DR PRIDE; Q9ULE3; -.
DR ProteomicsDB; 85008; -. [Q9ULE3-1]
DR ProteomicsDB; 85009; -. [Q9ULE3-2]
DR Antibodypedia; 32452; 39 antibodies from 13 providers.
DR DNASU; 27147; -.
DR Ensembl; ENST00000275884.10; ENSP00000275884.6; ENSG00000146966.13. [Q9ULE3-1]
DR Ensembl; ENST00000492720.5; ENSP00000419464.1; ENSG00000146966.13. [Q9ULE3-2]
DR Ensembl; ENST00000496613.6; ENSP00000419654.1; ENSG00000146966.13. [Q9ULE3-1]
DR Ensembl; ENST00000537639.5; ENSP00000442245.1; ENSG00000146966.13. [Q9ULE3-1]
DR GeneID; 27147; -.
DR KEGG; hsa:27147; -.
DR MANE-Select; ENST00000496613.6; ENSP00000419654.1; NM_015689.5; NP_056504.3.
DR UCSC; uc003vvw.3; human. [Q9ULE3-1]
DR CTD; 27147; -.
DR DisGeNET; 27147; -.
DR GeneCards; DENND2A; -.
DR HGNC; HGNC:22212; DENND2A.
DR HPA; ENSG00000146966; Low tissue specificity.
DR neXtProt; NX_Q9ULE3; -.
DR OpenTargets; ENSG00000146966; -.
DR PharmGKB; PA134931054; -.
DR VEuPathDB; HostDB:ENSG00000146966; -.
DR eggNOG; KOG3569; Eukaryota.
DR GeneTree; ENSGT00950000182931; -.
DR HOGENOM; CLU_008960_1_1_1; -.
DR InParanoid; Q9ULE3; -.
DR OMA; KPIFFRQ; -.
DR OrthoDB; 138384at2759; -.
DR PhylomeDB; Q9ULE3; -.
DR TreeFam; TF320336; -.
DR PathwayCommons; Q9ULE3; -.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; Q9ULE3; -.
DR BioGRID-ORCS; 27147; 15 hits in 1067 CRISPR screens.
DR ChiTaRS; DENND2A; human.
DR GenomeRNAi; 27147; -.
DR Pharos; Q9ULE3; Tbio.
DR PRO; PR:Q9ULE3; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9ULE3; protein.
DR Bgee; ENSG00000146966; Expressed in left uterine tube and 161 other tissues.
DR ExpressionAtlas; Q9ULE3; baseline and differential.
DR Genevisible; Q9ULE3; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR Gene3D; 3.40.50.11500; -; 1.
DR InterPro; IPR001194; cDENN_dom.
DR InterPro; IPR005112; dDENN_dom.
DR InterPro; IPR043153; DENN_C.
DR InterPro; IPR037516; Tripartite_DENN.
DR InterPro; IPR005113; uDENN_dom.
DR Pfam; PF03455; dDENN; 1.
DR Pfam; PF02141; DENN; 1.
DR Pfam; PF03456; uDENN; 1.
DR SMART; SM00801; dDENN; 1.
DR SMART; SM00799; DENN; 1.
DR SMART; SM00800; uDENN; 1.
DR PROSITE; PS50211; DENN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Cytoskeleton;
KW Guanine-nucleotide releasing factor; Phosphoprotein; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..1009
FT /note="DENN domain-containing protein 2A"
FT /id="PRO_0000242682"
FT DOMAIN 566..715
FT /note="uDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 737..870
FT /note="cDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 872..969
FT /note="dDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT REGION 15..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 171..334
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 434..479
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 498..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..63
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 77..100
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..150
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 218..248
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..291
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 297..313
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 443..463
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 515..532
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 551
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C4S8"
FT VAR_SEQ 776..800
FT /note="SILSKCCHAMVALIYPFAWQHTYIP -> RYPPWLLLLKRLNDSRSWTL
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019466"
FT VAR_SEQ 801..1009
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019467"
FT VARIANT 156
FT /note="P -> H (in dbSNP:rs269243)"
FT /evidence="ECO:0000269|PubMed:10574462,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_026856"
FT VARIANT 729
FT /note="E -> K (in dbSNP:rs2293177)"
FT /id="VAR_026857"
FT VARIANT 777
FT /note="I -> T (in dbSNP:rs6464833)"
FT /id="VAR_026858"
FT CONFLICT 600
FT /note="F -> L (in Ref. 3; AAH49193)"
FT /evidence="ECO:0000305"
FT CONFLICT 864
FT /note="A -> V (in Ref. 1; BAA86591)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1009 AA; 113853 MW; 4A596E6999F8AF3E CRC64;
MDMFSLDMII SDPAAEASRA GKKQLRGVQN PCPSARARPR HKSLNIKDKI SEWEGKKEVP
TPAPSRRADG QEDYLPSSTV ERRSSDGVRT QVTEAKNGMR PGTESTEKER NKGAVNVGGQ
DPEPGQDLSQ PEREVDPSWG RGREPRLGKL RFQNDPLSVL KQVKKLEQAL KDGSAGLDPQ
LPGTCYSPHC PPDKAEAGST LPENLGGGSG SEVSQRVHPS DLEGREPTPE LVEDRKGSCR
RPWDRSLENV YRGSEGSPTK PFINPLPKPR RTFKHAGEGD KDGKPGIGFR KEKRNLPPLP
SLPPPPLPSS PPPSSVNRRL WTGRQKSSAD HRKSYEFEDL LQSSSESSRV DWYAQTKLGL
TRTLSEENVY EDILDPPMKE NPYEDIELHG RCLGKKCVLN FPASPTSSIP DTLTKQSLSK
PAFFRQNSER RNFKLLDTRK LSRDGTGSPS KISPPSTPSS PDDIFFNLGD PQNGRKKRKI
PKLVLRINAI YEVRRGKKRV KRLSQSMESN SGKVTDENSE SDSDTEEKLK AHSQRLVNVK
SRLKQAPRYP SLARELIEYQ ERQLFEYFVV VSLHKKQAGA AYVPELTQQF PLKLERSFKF
MREAEDQLKA IPQFCFPDAK DWVPVQQFTS ETFSFVLTGE DGSRRFGYCR RLLPGGKGKR
LPEVYCIVSR LGCFSLFSRI LDEVEKRRGI SPALVQPLMR SVMEAPFPAL GKTILVKNFL
PGSGTEVIEL CRPLDSRLEH VDFESLFSSL SVRHLVCVFA SLLLERRVIF IADKLSILSK
CCHAMVALIY PFAWQHTYIP VLPPAMVDIV CSPTPFLIGL LSSSLPLLRE LPLEEVLVVD
LVNSRFLRQM DDEDSILPRK LQVALEHILE QRNELACEQD EGPLDGRHGP ESSPLNEVVS
EAFVRFFVEI VGHYSLFLTS GEREERTLQR EAFRKAVSSK SLRHFLEVFM ETQMFRGFIQ
ERELRRQDAK GLFEVRAQEY LETLPSGEHS GVNKFLKGLG NKMKFLHKK
