DEN1C_HUMAN
ID DEN1C_HUMAN Reviewed; 801 AA.
AC Q8IV53; B4E051; D3PFD4; Q8NDB1; Q9H5Z2;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=DENN domain-containing protein 1C;
DE AltName: Full=Connecdenn 3 {ECO:0000303|PubMed:20154091};
DE AltName: Full=Protein FAM31C;
GN Name=DENND1C; Synonyms=FAM31C;
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 2).
RC TISSUE=Ileal mucosa, and Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 430-801.
RC TISSUE=Lymph node;
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 [5]
RP IDENTIFICATION, SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH AP2A2;
RP CLTC AND RAB35.
RX PubMed=20154091; DOI=10.1074/jbc.m109.050930;
RA Marat A.L., McPherson P.S.;
RT "The connecdenn family, Rab35 guanine nucleotide exchange factors
RT interfacing with the clathrin machinery.";
RL J. Biol. Chem. 285:10627-10637(2010).
RN [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553, 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: Guanine nucleotide exchange factor (GEF) which may activate
CC RAB8A, RAB13 and RAB35. Promotes the exchange of GDP to GTP, converting
CC inactive GDP-bound Rab proteins into their active GTP-bound form.
CC {ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701}.
CC -!- SUBUNIT: Exhibits low nucleotide-independent RAB35-binding activity.
CC Interacts with clathrin heavy chain/CLTC and with AP2A2, but not with
CC AP2B1. {ECO:0000269|PubMed:20154091}.
CC -!- INTERACTION:
CC Q8IV53; O95295: SNAPIN; NbExp=3; IntAct=EBI-2871584, EBI-296723;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:20154091}.
CC Cytoplasmic vesicle, clathrin-coated vesicle
CC {ECO:0000269|PubMed:20154091}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IV53-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IV53-2; Sequence=VSP_040669;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15475.1; Type=Frameshift; 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; AK026410; BAB15475.1; ALT_FRAME; mRNA.
DR EMBL; AK303226; BAG64313.1; -; mRNA.
DR EMBL; CH471139; EAW69082.1; -; Genomic_DNA.
DR EMBL; BC033437; AAH33437.1; -; mRNA.
DR EMBL; AL834293; CAD38966.1; -; mRNA.
DR EMBL; BK006959; DAA12501.1; -; mRNA.
DR CCDS; CCDS45938.1; -. [Q8IV53-1]
DR CCDS; CCDS77225.1; -. [Q8IV53-2]
DR RefSeq; NP_001277260.1; NM_001290331.1. [Q8IV53-2]
DR RefSeq; NP_079174.2; NM_024898.3. [Q8IV53-1]
DR RefSeq; XP_006722969.1; XM_006722906.3. [Q8IV53-2]
DR RefSeq; XP_011526620.1; XM_011528318.2. [Q8IV53-2]
DR AlphaFoldDB; Q8IV53; -.
DR SMR; Q8IV53; -.
DR BioGRID; 123027; 7.
DR IntAct; Q8IV53; 4.
DR STRING; 9606.ENSP00000370889; -.
DR iPTMnet; Q8IV53; -.
DR PhosphoSitePlus; Q8IV53; -.
DR BioMuta; DENND1C; -.
DR DMDM; 74750652; -.
DR EPD; Q8IV53; -.
DR jPOST; Q8IV53; -.
DR MassIVE; Q8IV53; -.
DR MaxQB; Q8IV53; -.
DR PaxDb; Q8IV53; -.
DR PeptideAtlas; Q8IV53; -.
DR PRIDE; Q8IV53; -.
DR ProteomicsDB; 70662; -. [Q8IV53-1]
DR ProteomicsDB; 70663; -. [Q8IV53-2]
DR Antibodypedia; 50064; 63 antibodies from 14 providers.
DR DNASU; 79958; -.
DR Ensembl; ENST00000381480.7; ENSP00000370889.1; ENSG00000205744.10. [Q8IV53-1]
DR Ensembl; ENST00000543576.5; ENSP00000437805.1; ENSG00000205744.10. [Q8IV53-2]
DR GeneID; 79958; -.
DR KEGG; hsa:79958; -.
DR MANE-Select; ENST00000381480.7; ENSP00000370889.1; NM_024898.4; NP_079174.2.
DR UCSC; uc002mfe.4; human. [Q8IV53-1]
DR CTD; 79958; -.
DR GeneCards; DENND1C; -.
DR HGNC; HGNC:26225; DENND1C.
DR HPA; ENSG00000205744; Group enriched (bone marrow, intestine, lymphoid tissue).
DR MIM; 613634; gene.
DR neXtProt; NX_Q8IV53; -.
DR OpenTargets; ENSG00000205744; -.
DR PharmGKB; PA134893022; -.
DR VEuPathDB; HostDB:ENSG00000205744; -.
DR eggNOG; KOG3569; Eukaryota.
DR GeneTree; ENSGT00940000161573; -.
DR HOGENOM; CLU_008196_4_2_1; -.
DR InParanoid; Q8IV53; -.
DR OMA; PPILWQF; -.
DR OrthoDB; 189322at2759; -.
DR PhylomeDB; Q8IV53; -.
DR TreeFam; TF320336; -.
DR PathwayCommons; Q8IV53; -.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; Q8IV53; -.
DR BioGRID-ORCS; 79958; 18 hits in 1070 CRISPR screens.
DR ChiTaRS; DENND1C; human.
DR GenomeRNAi; 79958; -.
DR Pharos; Q8IV53; Tbio.
DR PRO; PR:Q8IV53; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8IV53; protein.
DR Bgee; ENSG00000205744; Expressed in granulocyte and 124 other tissues.
DR ExpressionAtlas; Q8IV53; baseline and differential.
DR Genevisible; Q8IV53; HS.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IBA:GO_Central.
DR GO; GO:0032456; P:endocytic recycling; IBA:GO_Central.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR Gene3D; 3.40.50.11500; -; 1.
DR InterPro; IPR001194; cDENN_dom.
DR InterPro; IPR005112; dDENN_dom.
DR InterPro; IPR043153; DENN_C.
DR InterPro; IPR040032; DENND1A/B/C.
DR InterPro; IPR037516; Tripartite_DENN.
DR InterPro; IPR005113; uDENN_dom.
DR PANTHER; PTHR13196; PTHR13196; 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; Cytoplasm; Cytoplasmic vesicle;
KW Guanine-nucleotide releasing factor; Phosphoprotein; Reference proteome.
FT CHAIN 1..801
FT /note="DENN domain-containing protein 1C"
FT /id="PRO_0000304676"
FT DOMAIN 13..157
FT /note="uDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 182..318
FT /note="cDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 320..398
FT /note="dDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT REGION 479..540
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 604..801
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 401..405
FT /note="FXDXF motif"
FT /evidence="ECO:0000250|UniProtKB:Q8TEH3"
FT MOTIF 558..567
FT /note="Clathrin box"
FT /evidence="ECO:0000250|UniProtKB:Q8TEH3"
FT COMPBIAS 619..664
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 689..704
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 705..719
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 726..740
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 751..765
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 772..789
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 553
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..44
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_040669"
FT VARIANT 23
FT /note="A -> T (in dbSNP:rs10416003)"
FT /id="VAR_035056"
FT VARIANT 489
FT /note="R -> C (in dbSNP:rs35001260)"
FT /id="VAR_035057"
FT VARIANT 542
FT /note="A -> V (in dbSNP:rs35810378)"
FT /id="VAR_035058"
FT CONFLICT 416
FT /note="S -> P (in Ref. 1; BAB15475)"
FT /evidence="ECO:0000305"
FT CONFLICT 601
FT /note="P -> L (in Ref. 1; BAB15475)"
FT /evidence="ECO:0000305"
FT CONFLICT 693
FT /note="S -> F (in Ref. 1; BAB15475)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 801 AA; 87065 MW; E8CCC5C6FCBADCDF CRC64;
MESRAEGGSP AVFDWFFEAA CPASLQEDPP ILRQFPPDFR DQEAMQMVPK FCFPFDVERE
PPSPAVQHFT FALTDLAGNR RFGFCRLRAG TQSCLCILSH LPWFEVFYKL LNTVGDLLAQ
DQVTEAEELL QNLFQQSLSG PQASVGLELG SGVTVSSGQG IPPPTRGNSK PLSCFVAPDS
GRLPSIPENR NLTELVVAVT DENIVGLFAA LLAERRVLLT ASKLSTLTSC VHASCALLYP
MRWEHVLIPT LPPHLLDYCC APMPYLIGVH ASLAERVREK ALEDVVVLNV DANTLETTFN
DVQALPPDVV SLLRLRLRKV ALAPGEGVSR LFLKAQALLF GGYRDALVCS PGQPVTFSEE
VFLAQKPGAP LQAFHRRAVH LQLFKQFIEA RLEKLNKGEG FSDQFEQEIT GCGASSGALR
SYQLWADNLK KGGGALLHSV KAKTQPAVKN MYRSAKSGLK GVQSLLMYKD GDSVLQRGGS
LRAPALPSRS DRLQQRLPIT QHFGKNRPLR PSRRRQLEEG TSEPPGAGTP PLSPEDEGCP
WAEEALDSSF LGSGEELDLL SEILDSLSMG AKSAGSLRPS QSLDCCHRGD LDSCFSLPNI
PRWQPDDKKL PEPEPQPLSL PSLQNASSLD ATSSSKDSRS QLIPSESDQE VTSPSQSSTA
SADPSIWGDP KPSPLTEPLI LHLTPSHKAA EDSTAQENPT PWLSTAPTEP SPPESPQILA
PTKPNFDIAW TSQPLDPSSD PSSLEDPRAR PPKALLAERA HLQPREEPGA LNSPATPTSN
CQKSQPSSRP RVADLKKCFE G
