ID   DEN2C_HUMAN             Reviewed;         928 AA.
AC   Q68D51; B1AL26; Q5TCX6; Q6P3R3;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   27-JUN-2006, sequence version 2.
DT   02-OCT-2024, entry version 140.
DE   RecName: Full=DENN domain-containing protein 2C;
GN   Name=DENND2C;
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] (ISOFORMS 1 AND 3), AND VARIANTS
RP   GLU-2 AND GLY-170.
RC   TISSUE=Testis;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [2]
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLU-2.
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   [4]
RP   FUNCTION AS GUANYL-NUCLEOTIDE EXCHANGE FACTOR.
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).
RN   [5]
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).
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.
CC       {ECO:0000269|PubMed:20937701}.
CC   -!- INTERACTION:
CC       Q68D51-2; O76024: WFS1; NbExp=3; IntAct=EBI-13075846, EBI-720609;
CC       Q68D51-2; P07947: YES1; NbExp=3; IntAct=EBI-13075846, EBI-515331;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q68D51-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q68D51-2; Sequence=VSP_019468;
CC       Name=3;
CC         IsoId=Q68D51-3; Sequence=VSP_036782;
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DR   EMBL; BX647950; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; CR749576; CAH18369.1; -; mRNA.
DR   EMBL; AL133382; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC063894; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS58018.1; -. [Q68D51-1]
DR   CCDS; CCDS875.1; -. [Q68D51-3]
DR   RefSeq; NP_001243333.1; NM_001256404.1. [Q68D51-1]
DR   RefSeq; NP_940861.3; NM_198459.3. [Q68D51-3]
DR   AlphaFoldDB; Q68D51; -.
DR   SMR; Q68D51; -.
DR   BioGRID; 127862; 14.
DR   IntAct; Q68D51; 10.
DR   STRING; 9606.ENSP00000376955; -.
DR   GlyCosmos; Q68D51; 1 site, 1 glycan.
DR   GlyGen; Q68D51; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q68D51; -.
DR   PhosphoSitePlus; Q68D51; -.
DR   BioMuta; DENND2C; -.
DR   DMDM; 109825713; -.
DR   jPOST; Q68D51; -.
DR   MassIVE; Q68D51; -.
DR   PaxDb; 9606-ENSP00000376955; -.
DR   PeptideAtlas; Q68D51; -.
DR   ProteomicsDB; 66050; -. [Q68D51-1]
DR   ProteomicsDB; 66051; -. [Q68D51-2]
DR   ProteomicsDB; 66052; -. [Q68D51-3]
DR   Antibodypedia; 33861; 100 antibodies from 17 providers.
DR   DNASU; 163259; -.
DR   Ensembl; ENST00000393274.6; ENSP00000376955.1; ENSG00000175984.16. [Q68D51-1]
DR   Ensembl; ENST00000393276.7; ENSP00000376957.3; ENSG00000175984.16. [Q68D51-3]
DR   GeneID; 163259; -.
DR   KEGG; hsa:163259; -.
DR   MANE-Select; ENST00000393274.6; ENSP00000376955.1; NM_001256404.2; NP_001243333.1.
DR   UCSC; uc001efc.2; human. [Q68D51-1]
DR   AGR; HGNC:24748; -.
DR   CTD; 163259; -.
DR   DisGeNET; 163259; -.
DR   GeneCards; DENND2C; -.
DR   HGNC; HGNC:24748; DENND2C.
DR   HPA; ENSG00000175984; Tissue enhanced (esophagus, skeletal muscle).
DR   neXtProt; NX_Q68D51; -.
DR   OpenTargets; ENSG00000175984; -.
DR   PharmGKB; PA142671985; -.
DR   VEuPathDB; HostDB:ENSG00000175984; -.
DR   eggNOG; KOG3569; Eukaryota.
DR   GeneTree; ENSGT00950000182931; -.
DR   HOGENOM; CLU_008960_2_0_1; -.
DR   InParanoid; Q68D51; -.
DR   OMA; PDSKDWI; -.
DR   OrthoDB; 5398783at2759; -.
DR   PhylomeDB; Q68D51; -.
DR   TreeFam; TF320336; -.
DR   PathwayCommons; Q68D51; -.
DR   Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR   SignaLink; Q68D51; -.
DR   BioGRID-ORCS; 163259; 20 hits in 1146 CRISPR screens.
DR   ChiTaRS; DENND2C; human.
DR   GenomeRNAi; 163259; -.
DR   Pharos; Q68D51; Tbio.
DR   PRO; PR:Q68D51; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q68D51; protein.
DR   Bgee; ENSG00000175984; Expressed in esophagus squamous epithelium and 149 other cell types or tissues.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR   Gene3D; 3.30.450.200; -; 1.
DR   Gene3D; 3.40.50.11500; -; 1.
DR   InterPro; IPR001194; cDENN_dom.
DR   InterPro; IPR005112; dDENN_dom.
DR   InterPro; IPR043153; DENN_C.
DR   InterPro; IPR051942; DENN_domain_containing_2.
DR   InterPro; IPR037516; Tripartite_DENN.
DR   InterPro; IPR005113; uDENN_dom.
DR   PANTHER; PTHR15288; DENN DOMAIN-CONTAINING PROTEIN 2; 1.
DR   PANTHER; PTHR15288:SF6; DENN DOMAIN-CONTAINING PROTEIN 2C; 1.
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; Guanine-nucleotide releasing factor; Phosphoprotein;
KW   Proteomics identification; Reference proteome.
FT   CHAIN           1..928
FT                   /note="DENN domain-containing protein 2C"
FT                   /id="PRO_0000242684"
FT   DOMAIN          492..641
FT                   /note="uDENN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT   DOMAIN          663..796
FT                   /note="cDENN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT   DOMAIN          798..888
FT                   /note="dDENN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT   REGION          67..105
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          245..266
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          428..456
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        83..105
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         271
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6P9P8"
FT   VAR_SEQ         354..410
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:17974005"
FT                   /id="VSP_036782"
FT   VAR_SEQ         642..753
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_019468"
FT   VARIANT         2
FT                   /note="D -> E (in dbSNP:rs7541738)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:17974005"
FT                   /id="VAR_026859"
FT   VARIANT         170
FT                   /note="D -> G (in dbSNP:rs12136548)"
FT                   /evidence="ECO:0000269|PubMed:17974005"
FT                   /id="VAR_026860"
FT   CONFLICT        392
FT                   /note="K -> Q (in Ref. 1; CAH18369)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        769
FT                   /note="A -> T (in Ref. 1; BX647950)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        774
FT                   /note="Q -> H (in Ref. 1; CAH18369)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   928 AA;  106865 MW;  2B450938D2199731 CRC64;
     MDVGFSRTTV QTLSRSHCKN IKQKISQWEG RANGISNPEK WCPKDFGVRY NCHQEIRLKK
     NPIAERKSKN LDVTSRENVG LDINENTKSH DQSENENKKH EYDDTHFFKN ESESNWVCSR
     VKEIESCKED VLDPETSLPP GNFYTSQILW KKIEALPPDK LLNLALEHCD SSEKELNFRV
     LDSSYGITKS LENIYSEPEG QECGPSINPL PKPRRTFRYL SESGVTPYKE RNCDKKYCEN
     NSCAQSSLAS SQEPEPKKYG GKIRGRSKRK SFEFEDIQHF RNRNSQTIRE ELGRNSGSAL
     YYTQSEDNIY EDIIYPTKEN PYEDIPVQPL PMWRSPSAWK LPPAKSAFKA PKLPPKPQFL
     HRKTMEVKNS QAYLRSKLTK DTTLPVTLTE WKLFRAGEVA NTKRKNLPRL VLKIDDIFES
     KRGKKKVKLH SYTGKELPPT KGETSGNESD AEYLPKNRHK RLAQLQPSSK RNPHYQTLER
     DLIELQEQQL FELFVVVSLQ KKPSGISYIP QVIQQFPGKD DHGYKQSKDM EERLKVIPKF
     CFPDSKDWMP TSELKSETFS FVLTGEDGSR WFGYCKKLLP VGKGKRLPEV YCMVSRLGCF
     NLFSKILDEV EKRREMSPAL VYPFMRSVME APFPAPGRTI TVKSYLPGAG DESIELCRPL
     DSRLEHVDFK CLFKCLSVCH LIRVCASLLL ERRVIFVANS LSTLSKCGHA VVATLYPFTW
     QHTYIPVLPA SMIDIVCSPT PFLIGILSCS LPQLQDLPIE EVLIVDLCAD KFLQEVSDED
     EILPPKLQAA LMQILEERNE ILTQEQNFSQ DVTLNSLVSE AFVRFFVELV GHYSLNMTVT
     ERGERVFQRE PFRKSHTSRS VRHFLDLFME TQMFAGFIQD RELRKSGVKG LFEIRAIQYL
     ETIPESEPSG MNRILRSLGS KMKFLQKK
//