DEN10_HUMAN
ID DEN10_HUMAN Reviewed; 357 AA.
AC Q8TCE6; B1AMV6; B4DDC3; D3DRC8; Q9NXW4;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=DENN domain-containing protein 10 {ECO:0000305};
DE AltName: Full=Protein FAM45A;
GN Name=DENND10 {ECO:0000312|HGNC:HGNC:31793};
GN Synonyms=FAM45A {ECO:0000312|HGNC:HGNC:31793};
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=Adipose tissue;
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].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RAB27A AND RAB27B.
RX PubMed=30771381; DOI=10.1016/j.bbamcr.2019.02.006;
RA Zhang J., Zhang K., Qi L., Hu Q., Shen Z., Liu B., Deng J., Zhang C.,
RA Zhang Y.;
RT "DENN domain-containing protein FAM45A regulates the homeostasis of
RT late/multivesicular endosomes.";
RL Biochim. Biophys. Acta 1866:916-929(2019).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) regulating
CC homeostasis of late endocytic pathway, including endosomal positioning,
CC maturation and secretion, possibly through activating Rab proteins such
CC as RAB27A and RAB27B. Seems to promote the exchange of GDP to GTP,
CC converting inactive GDP-bound RAB27A and RAB27B into their active GTP-
CC bound form. {ECO:0000269|PubMed:30771381}.
CC -!- SUBUNIT: Interacts with RAB27A and RAB27B (GDP-bound forms
CC preferentially). {ECO:0000269|PubMed:30771381}.
CC -!- SUBCELLULAR LOCATION: Late endosome {ECO:0000269|PubMed:30771381}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TCE6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TCE6-2; Sequence=VSP_038301;
CC -!- SIMILARITY: Belongs to the DENND10 family. {ECO:0000305}.
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DR EMBL; AK000031; BAA90894.1; -; mRNA.
DR EMBL; AK293136; BAG56684.1; -; mRNA.
DR EMBL; AL355598; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49406.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49407.1; -; Genomic_DNA.
DR EMBL; BC022271; AAH22271.1; -; mRNA.
DR CCDS; CCDS7609.1; -. [Q8TCE6-1]
DR RefSeq; NP_001290040.1; NM_001303111.1. [Q8TCE6-2]
DR RefSeq; NP_001290041.1; NM_001303112.1.
DR RefSeq; NP_001290042.1; NM_001303113.1.
DR RefSeq; NP_996892.1; NM_207009.3. [Q8TCE6-1]
DR RefSeq; XP_016871750.1; XM_017016261.1. [Q8TCE6-2]
DR RefSeq; XP_016871751.1; XM_017016262.1. [Q8TCE6-2]
DR RefSeq; XP_016871752.1; XM_017016263.1. [Q8TCE6-2]
DR AlphaFoldDB; Q8TCE6; -.
DR BioGRID; 135667; 34.
DR IntAct; Q8TCE6; 26.
DR MINT; Q8TCE6; -.
DR STRING; 9606.ENSP00000354688; -.
DR iPTMnet; Q8TCE6; -.
DR PhosphoSitePlus; Q8TCE6; -.
DR BioMuta; FAM45A; -.
DR DMDM; 51316043; -.
DR EPD; Q8TCE6; -.
DR jPOST; Q8TCE6; -.
DR MassIVE; Q8TCE6; -.
DR MaxQB; Q8TCE6; -.
DR PaxDb; Q8TCE6; -.
DR PeptideAtlas; Q8TCE6; -.
DR PRIDE; Q8TCE6; -.
DR ProteomicsDB; 74125; -. [Q8TCE6-1]
DR ProteomicsDB; 74126; -. [Q8TCE6-2]
DR Antibodypedia; 49417; 49 antibodies from 14 providers.
DR DNASU; 404636; -.
DR Ensembl; ENST00000361432.3; ENSP00000354688.2; ENSG00000119979.18. [Q8TCE6-1]
DR GeneID; 404636; -.
DR KEGG; hsa:404636; -.
DR MANE-Select; ENST00000361432.3; ENSP00000354688.2; NM_207009.4; NP_996892.1.
DR UCSC; uc001ldw.5; human. [Q8TCE6-1]
DR CTD; 404636; -.
DR GeneCards; DENND10; -.
DR HGNC; HGNC:31793; DENND10.
DR HPA; ENSG00000119979; Low tissue specificity.
DR neXtProt; NX_Q8TCE6; -.
DR VEuPathDB; HostDB:ENSG00000119979; -.
DR eggNOG; ENOG502QVHR; Eukaryota.
DR GeneTree; ENSGT00390000014431; -.
DR HOGENOM; CLU_050301_0_0_1; -.
DR InParanoid; Q8TCE6; -.
DR OMA; VKMMEAY; -.
DR OrthoDB; 1065142at2759; -.
DR PhylomeDB; Q8TCE6; -.
DR TreeFam; TF332501; -.
DR PathwayCommons; Q8TCE6; -.
DR SignaLink; Q8TCE6; -.
DR BioGRID-ORCS; 404636; 33 hits in 1080 CRISPR screens.
DR ChiTaRS; FAM45A; human.
DR GenomeRNAi; 404636; -.
DR Pharos; Q8TCE6; Tdark.
DR PRO; PR:Q8TCE6; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q8TCE6; protein.
DR Bgee; ENSG00000119979; Expressed in monocyte and 94 other tissues.
DR ExpressionAtlas; Q8TCE6; baseline and differential.
DR Genevisible; Q8TCE6; HS.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0032509; P:endosome transport via multivesicular body sorting pathway; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IMP:UniProtKB.
DR GO; GO:2000641; P:regulation of early endosome to late endosome transport; IMP:UniProtKB.
DR InterPro; IPR042431; FAM45.
DR InterPro; IPR037516; Tripartite_DENN.
DR PANTHER; PTHR28544; PTHR28544; 1.
DR PROSITE; PS50211; DENN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endosome; Guanine-nucleotide releasing factor;
KW Reference proteome.
FT CHAIN 1..357
FT /note="DENN domain-containing protein 10"
FT /id="PRO_0000187034"
FT DOMAIN 1..140
FT /note="uDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 165..299
FT /note="cDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 301..357
FT /note="dDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT VAR_SEQ 1..18
FT /note="MAAAEVADTQLMLGVGLI -> MLSSDHLSTV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038301"
FT CONFLICT 267
FT /note="K -> R (in Ref. 1; BAA90894)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 357 AA; 40513 MW; B4AE072A5D9DB379 CRC64;
MAAAEVADTQ LMLGVGLIEK DTNGEVLWVW CYPSTTATLR NLLLRKCCLT DENKLLHPFV
FGQYRRTWFY ITTIEVPDSS ILKKVTHFSI VLTAKDFNPE KYAAFTRILC RMYLKHGSPV
KMMESYIAVL TKGICQSEEN GSFLSKDFDA RKAYLAGSIK DIVSQFGMET VILHTALMLK
KRIVVYHPKI EAVQEFTRTL PALVWHRQDW TILHSYVHLN ADELEALQMC TGYVAGFVDL
EVSNRPDLYD VFVNLAESEI TIAPLAKEAM AMGKLHKEMG QLIVQSAEDP EKSESHVIQD
IALKTREIFT NLAPFSEVSA DGEKRVLNLE ALKQKRFPPA TENFLYHLAA AEQMLKI