DEN6A_HUMAN
ID DEN6A_HUMAN Reviewed; 608 AA.
AC Q8IWF6; Q7Z5T4; Q8N235; Q8TEG8;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Protein DENND6A;
DE AltName: Full=DENN domain-containing protein 6A;
GN Name=DENND6A; Synonyms=FAM116A;
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=Spleen;
RX PubMed=12693554; DOI=10.1093/dnares/10.1.49;
RA Jikuya H., Takano J., Kikuno R., Hirosawa M., Nagase T., Nomura N.,
RA Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen. II. The
RT complete sequences of 81 cDNA clones.";
RL DNA Res. 10:49-57(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis, and Uterus;
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 177-608.
RC TISSUE=Tongue;
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 [5]
RP IDENTIFICATION.
RX PubMed=21330364; DOI=10.1074/jbc.r110.217067;
RA Marat A.L., Dokainish H., McPherson P.S.;
RT "DENN domain proteins: regulators of Rab GTPases.";
RL J. Biol. Chem. 286:13791-13800(2011).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22595670; DOI=10.1016/j.devcel.2012.04.010;
RA Linford A., Yoshimura S., Nunes Bastos R., Langemeyer L., Gerondopoulos A.,
RA Rigden D.J., Barr F.A.;
RT "Rab14 and its exchange factor FAM116 link endocytic recycling and adherens
RT junction stability in migrating cells.";
RL Dev. Cell 22:952-966(2012).
RN [8]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-510, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) for RAB14. Component
CC of an endocytic recycling pathway that is required for the control of
CC ADAM10 transport, shedding of N-cadherin/CDH2 by ADAM9 or ADAM10 and
CC regulation of cell-cell junctions. Required for RAB14 recruitment to
CC recycling endosomes. {ECO:0000269|PubMed:22595670}.
CC -!- SUBCELLULAR LOCATION: Recycling endosome {ECO:0000269|PubMed:22595670}.
CC Cytoplasm {ECO:0000269|PubMed:22595670}.
CC -!- SIMILARITY: Belongs to the DENND6 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB84982.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC03852.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK074156; BAB84982.1; ALT_INIT; mRNA.
DR EMBL; AC114480; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC040291; AAH40291.1; -; mRNA.
DR EMBL; BC054343; AAH54343.1; -; mRNA.
DR EMBL; AK092288; BAC03852.1; ALT_INIT; mRNA.
DR CCDS; CCDS33773.1; -.
DR RefSeq; NP_689891.1; NM_152678.2.
DR AlphaFoldDB; Q8IWF6; -.
DR BioGRID; 128398; 86.
DR IntAct; Q8IWF6; 15.
DR STRING; 9606.ENSP00000311401; -.
DR iPTMnet; Q8IWF6; -.
DR PhosphoSitePlus; Q8IWF6; -.
DR BioMuta; DENND6A; -.
DR DMDM; 74728180; -.
DR EPD; Q8IWF6; -.
DR jPOST; Q8IWF6; -.
DR MassIVE; Q8IWF6; -.
DR MaxQB; Q8IWF6; -.
DR PaxDb; Q8IWF6; -.
DR PeptideAtlas; Q8IWF6; -.
DR PRIDE; Q8IWF6; -.
DR ProteomicsDB; 70853; -.
DR Antibodypedia; 31568; 51 antibodies from 15 providers.
DR DNASU; 201627; -.
DR Ensembl; ENST00000311128.10; ENSP00000311401.5; ENSG00000174839.13.
DR GeneID; 201627; -.
DR KEGG; hsa:201627; -.
DR MANE-Select; ENST00000311128.10; ENSP00000311401.5; NM_152678.3; NP_689891.1.
DR UCSC; uc003dja.4; human.
DR CTD; 201627; -.
DR DisGeNET; 201627; -.
DR GeneCards; DENND6A; -.
DR HGNC; HGNC:26635; DENND6A.
DR HPA; ENSG00000174839; Low tissue specificity.
DR neXtProt; NX_Q8IWF6; -.
DR OpenTargets; ENSG00000174839; -.
DR PharmGKB; PA144596431; -.
DR VEuPathDB; HostDB:ENSG00000174839; -.
DR eggNOG; KOG2432; Eukaryota.
DR GeneTree; ENSGT00390000005529; -.
DR HOGENOM; CLU_017013_0_1_1; -.
DR InParanoid; Q8IWF6; -.
DR OMA; EANLEHW; -.
DR OrthoDB; 252077at2759; -.
DR PhylomeDB; Q8IWF6; -.
DR TreeFam; TF320228; -.
DR PathwayCommons; Q8IWF6; -.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; Q8IWF6; -.
DR BioGRID-ORCS; 201627; 16 hits in 1080 CRISPR screens.
DR ChiTaRS; DENND6A; human.
DR GenomeRNAi; 201627; -.
DR Pharos; Q8IWF6; Tbio.
DR PRO; PR:Q8IWF6; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8IWF6; protein.
DR Bgee; ENSG00000174839; Expressed in germinal epithelium of ovary and 195 other tissues.
DR ExpressionAtlas; Q8IWF6; baseline and differential.
DR Genevisible; Q8IWF6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:2000049; P:positive regulation of cell-cell adhesion mediated by cadherin; IDA:UniProtKB.
DR InterPro; IPR018307; ABL9/DENND6_dom.
DR InterPro; IPR024224; DENND6.
DR InterPro; IPR037516; Tripartite_DENN.
DR PANTHER; PTHR13677; PTHR13677; 1.
DR Pfam; PF09794; Avl9; 1.
DR PROSITE; PS50211; DENN; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Endosome; Guanine-nucleotide releasing factor; Methylation;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..608
FT /note="Protein DENND6A"
FT /id="PRO_0000289116"
FT DOMAIN 63..247
FT /note="uDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 273..393
FT /note="cDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 395..528
FT /note="dDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 127
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 510
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CONFLICT 229
FT /note="G -> A (in Ref. 1; BAB84982)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 608 AA; 69575 MW; A0DFC75B7E4796BF CRC64;
MALRGPAGLG PGSRRPLDEA VAGAEGREAP ALVAAGGAPE DDEEDDGRGR GLLRWDSFSA
WLHCVCVVGF DLELGQAVEV IYPQHSKLTD REKTNICYLS FPDSNSGCLG DTQFCFRFRQ
SSGRRVSLHC LLDQFDKDLP VYLKKDPAYF YGYVYFRQVR DKTLKRGYFQ KSLVLISKLP
YIHFFHTVLK QIAPEYFEKN EPYLEAACND VDRWPAPVPG KTLHLPIMGV VMKVRIPTCH
DKPGTTQIVQ LTQQVDTNIS VILPTVHEVD IFRCFCPVFL HSQMLWELVL LGEPLVVMAP
SPSESSETVL ALVNCISPLK YFSDFRPYFT IHDSEFKEYT TRTQAPPSVI LGVTNPFFAK
TLQHWPHIIR IGDLKPTGEI PKQVKVKKLK NLKTLDSKPG VYTSYKPYLN RDEEIIKQLQ
KGVQQKRPSE AQSVILRRYF LELTQSFIIP LERYVASLMP LQKSISPWKS PPQLRQFLPE
EFMKTLEKTG PQLTSRIKGD WIGLYRHFLK SPNFDGWFKT RRKEMTQKLE ALHLEALCEE
DLLLWIQKHT EVETVDLVLK LKNKLLQADR EHLPVKPDTM EKLRTHIDAI ILALPEDLQG
ILLKTGMT
