CL16A_HUMAN
ID CL16A_HUMAN Reviewed; 1053 AA.
AC Q2KHT3; O15058; Q6ZTB2;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Protein CLEC16A {ECO:0000305};
DE AltName: Full=C-type lectin domain family 16 member A {ECO:0000312|HGNC:HGNC:29013};
GN Name=CLEC16A {ECO:0000312|HGNC:HGNC:29013}; Synonyms=KIAA0350;
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).
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Cerebellum;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lymph;
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 INVOLVEMENT IN IDDM, AND TISSUE SPECIFICITY.
RX PubMed=17632545; DOI=10.1038/nature06010;
RA Hakonarson H., Grant S.F.A., Bradfield J.P., Marchand L., Kim C.E.,
RA Glessner J.T., Grabs R., Casalunovo T., Taback S.P., Frackelton E.C.,
RA Lawson M.L., Robinson L.J., Skraban R., Lu Y., Chiavacci R.M.,
RA Stanley C.A., Kirsch S.E., Rappaport E.F., Orange J.S., Monos D.S.,
RA Devoto M., Qu H.-Q., Polychronakos C.;
RT "A genome-wide association study identifies KIAA0350 as a type 1 diabetes
RT gene.";
RL Nature 448:591-594(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INVOLVEMENT IN IDDM.
RX PubMed=24949970; DOI=10.1016/j.cell.2014.05.016;
RA Soleimanpour S.A., Gupta A., Bakay M., Ferrari A.M., Groff D.N.,
RA Fadista J., Spruce L.A., Kushner J.A., Groop L., Seeholzer S.H.,
RA Kaufman B.A., Hakonarson H., Stoffers D.A.;
RT "The diabetes susceptibility gene Clec16a regulates mitophagy.";
RL Cell 157:1577-1590(2014).
CC -!- FUNCTION: Regulator of mitophagy through the upstream regulation of the
CC RNF41/NRDP1-PRKN pathway. Mitophagy is a selective form of autophagy
CC necessary for mitochondrial quality control. The RNF41/NRDP1-PRKN
CC pathway regulates autophagosome-lysosome fusion during late mitophagy.
CC May protect RNF41/NRDP1 from proteosomal degradation, RNF41/NRDP1 which
CC regulates proteosomal degradation of PRKN. Plays a key role in beta
CC cells functions by regulating mitophagy/autophagy and mitochondrial
CC health. {ECO:0000269|PubMed:24949970}.
CC -!- SUBUNIT: Interacts with RNF41/NRDP1. {ECO:0000250|UniProtKB:Q80U30}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:Q80U30};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q80U30}. Lysosome
CC membrane {ECO:0000250|UniProtKB:Q80U30}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q80U30}. Note=Associates with the endolysosome
CC membrane. {ECO:0000250|UniProtKB:Q80U30}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q2KHT3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q2KHT3-2; Sequence=VSP_022746, VSP_022747, VSP_022748,
CC VSP_022750;
CC Name=3;
CC IsoId=Q2KHT3-3; Sequence=VSP_022745, VSP_022749;
CC -!- TISSUE SPECIFICITY: Almost exclusively expressed in immune cells,
CC including dendritic cells, B-lymphocytes and natural killer cells.
CC {ECO:0000269|PubMed:17632545}.
CC -!- DISEASE: Diabetes mellitus, insulin-dependent (IDDM) [MIM:222100]: A
CC multifactorial disorder of glucose homeostasis that is characterized by
CC susceptibility to ketoacidosis in the absence of insulin therapy.
CC Clinical features are polydipsia, polyphagia and polyuria which result
CC from hyperglycemia-induced osmotic diuresis and secondary thirst. These
CC derangements result in long-term complications that affect the eyes,
CC kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:17632545,
CC ECO:0000269|PubMed:24949970}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry. Three
CC common non-coding variants of CLEC16A in strong linkage disequilibrium
CC reach genome-wide significance for association with the disease
CC (PubMed:17632545). The non-coding variant rs12708716 is associated with
CC reduced expression of CLEC16A in beta cells and reduced beta cell
CC function (PubMed:24949970). {ECO:0000269|PubMed:17632545,
CC ECO:0000269|PubMed:24949970}.
CC -!- SIMILARITY: Belongs to the CLEC16A/gop-1 family. {ECO:0000305}.
CC -!- CAUTION: Despite its name, does not contain a C-type lectin domain.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA20807.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB002348; BAA20807.3; ALT_INIT; mRNA.
DR EMBL; AK126771; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC112897; AAI12898.1; -; mRNA.
DR CCDS; CCDS45409.1; -. [Q2KHT3-1]
DR CCDS; CCDS58423.1; -. [Q2KHT3-2]
DR RefSeq; NP_001230332.1; NM_001243403.1. [Q2KHT3-2]
DR RefSeq; NP_056041.1; NM_015226.2. [Q2KHT3-1]
DR AlphaFoldDB; Q2KHT3; -.
DR BioGRID; 116875; 17.
DR IntAct; Q2KHT3; 6.
DR STRING; 9606.ENSP00000387122; -.
DR GlyGen; Q2KHT3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q2KHT3; -.
DR PhosphoSitePlus; Q2KHT3; -.
DR BioMuta; CLEC16A; -.
DR DMDM; 125950459; -.
DR EPD; Q2KHT3; -.
DR jPOST; Q2KHT3; -.
DR MassIVE; Q2KHT3; -.
DR MaxQB; Q2KHT3; -.
DR PaxDb; Q2KHT3; -.
DR PeptideAtlas; Q2KHT3; -.
DR PRIDE; Q2KHT3; -.
DR ProteomicsDB; 61309; -. [Q2KHT3-1]
DR ProteomicsDB; 61310; -. [Q2KHT3-2]
DR ProteomicsDB; 61311; -. [Q2KHT3-3]
DR Antibodypedia; 24665; 218 antibodies from 30 providers.
DR DNASU; 23274; -.
DR Ensembl; ENST00000409552.4; ENSP00000386495.3; ENSG00000038532.16. [Q2KHT3-2]
DR Ensembl; ENST00000409790.6; ENSP00000387122.1; ENSG00000038532.16. [Q2KHT3-1]
DR GeneID; 23274; -.
DR KEGG; hsa:23274; -.
DR MANE-Select; ENST00000409790.6; ENSP00000387122.1; NM_015226.3; NP_056041.1.
DR UCSC; uc002dan.5; human. [Q2KHT3-1]
DR CTD; 23274; -.
DR DisGeNET; 23274; -.
DR GeneCards; CLEC16A; -.
DR HGNC; HGNC:29013; CLEC16A.
DR HPA; ENSG00000038532; Low tissue specificity.
DR MIM; 222100; phenotype.
DR MIM; 611303; gene.
DR neXtProt; NX_Q2KHT3; -.
DR OpenTargets; ENSG00000038532; -.
DR PharmGKB; PA162382340; -.
DR VEuPathDB; HostDB:ENSG00000038532; -.
DR eggNOG; KOG2219; Eukaryota.
DR GeneTree; ENSGT00390000013826; -.
DR HOGENOM; CLU_007413_1_0_1; -.
DR InParanoid; Q2KHT3; -.
DR OMA; FMFDDHI; -.
DR OrthoDB; 1319544at2759; -.
DR PhylomeDB; Q2KHT3; -.
DR TreeFam; TF314293; -.
DR PathwayCommons; Q2KHT3; -.
DR SignaLink; Q2KHT3; -.
DR BioGRID-ORCS; 23274; 16 hits in 1079 CRISPR screens.
DR ChiTaRS; CLEC16A; human.
DR GeneWiki; CLEC16A; -.
DR GenomeRNAi; 23274; -.
DR Pharos; Q2KHT3; Tbio.
DR PRO; PR:Q2KHT3; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q2KHT3; protein.
DR Bgee; ENSG00000038532; Expressed in left testis and 138 other tissues.
DR ExpressionAtlas; Q2KHT3; baseline and differential.
DR Genevisible; Q2KHT3; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0036020; C:endolysosome membrane; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0009267; P:cellular response to starvation; IMP:UniProtKB.
DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central.
DR GO; GO:0008333; P:endosome to lysosome transport; IBA:GO_Central.
DR GO; GO:1901097; P:negative regulation of autophagosome maturation; IMP:UniProtKB.
DR GO; GO:1904766; P:negative regulation of macroautophagy by TORC1 signaling; IMP:UniProtKB.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:1901096; P:regulation of autophagosome maturation; IBA:GO_Central.
DR InterPro; IPR039272; CLEC16A/TT9.
DR InterPro; IPR019155; CLEC16A/TT9_N.
DR InterPro; IPR045820; CLEC16A_C.
DR PANTHER; PTHR21481; PTHR21481; 1.
DR Pfam; PF19439; CLEC16A_C; 1.
DR Pfam; PF09758; FPL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Diabetes mellitus; Endosome; Lysosome;
KW Membrane; Reference proteome.
FT CHAIN 1..1053
FT /note="Protein CLEC16A"
FT /id="PRO_0000274476"
FT DOMAIN 51..198
FT /note="FPL"
FT /evidence="ECO:0000255"
FT REGION 375..434
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 451..471
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 892..983
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 409..434
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 892..936
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 969..983
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..913
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_022745"
FT VAR_SEQ 201..202
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022746"
FT VAR_SEQ 419..434
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022747"
FT VAR_SEQ 882..924
FT /note="FAVAQCINQHSSPSLSSQSPPSASGSPSGSGSTSHCDSGGTSS -> EPAPR
FT PAPQLVHHGGRSRSFSLWSLCELPFLSQKPRRLAAPAS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022748"
FT VAR_SEQ 914..935
FT /note="TSHCDSGGTSSSSTPSTAQSPA -> MAATGFSAPNGSCHGTSRTVNS (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_022749"
FT VAR_SEQ 925..1053
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022750"
FT VARIANT 906
FT /note="G -> E (in dbSNP:rs2241100)"
FT /id="VAR_030288"
SQ SEQUENCE 1053 AA; 117715 MW; 89DE7C0AE228B0D9 CRC64;
MFGRSRSWVG GGHGKTSRNI HSLDHLKYLY HVLTKNTTVT EQNRNLLVET IRSITEILIW
GDQNDSSVFD FFLEKNMFVF FLNILRQKSG RYVCVQLLQT LNILFENISH ETSLYYLLSN
NYVNSIIVHK FDFSDEEIMA YYISFLKTLS LKLNNHTVHF FYNEHTNDFA LYTEAIKFFN
HPESMVRIAV RTITLNVYKV SLDNQAMLHY IRDKTAVPYF SNLVWFIGSH VIELDDCVQT
DEEHRNRGKL SDLVAEHLDH LHYLNDILII NCEFLNDVLT DHLLNRLFLP LYVYSLENQD
KGGERPKISL PVSLYLLSQV FLIIHHAPLV NSLAEVILNG DLSEMYAKTE QDIQRSSAKP
SIRCFIKPTE TLERSLEMNK HKGKRRVQKR PNYKNVGEEE DEEKGPTEDA QEDAEKAKGT
EGGSKGIKTS GESEEIEMVI MERSKLSELA ASTSVQEQNT TDEEKSAAAT CSESTQWSRP
FLDMVYHALD SPDDDYHALF VLCLLYAMSH NKGMDPEKLE RIQLPVPNAA EKTTYNHPLA
ERLIRIMNNA AQPDGKIRLA TLELSCLLLK QQVLMSAGCI MKDVHLACLE GAREESVHLV
RHFYKGEDIF LDMFEDEYRS MTMKPMNVEY LMMDASILLP PTGTPLTGID FVKRLPCGDV
EKTRRAIRVF FMLRSLSLQL RGEPETQLPL TREEDLIKTD DVLDLNNSDL IACTVITKDG
GMVQRFLAVD IYQMSLVEPD VSRLGWGVVK FAGLLQDMQV TGVEDDSRAL NITIHKPASS
PHSKPFPILQ ATFIFSDHIR CIIAKQRLAK GRIQARRMKM QRIAALLDLP IQPTTEVLGF
GLGSSTSTQH LPFRFYDQGR RGSSDPTVQR SVFASVDKVP GFAVAQCINQ HSSPSLSSQS
PPSASGSPSG SGSTSHCDSG GTSSSSTPST AQSPADAPMS PELPKPHLPD QLVIVNETEA
DSKPSKNVAR SAAVETASLS PSLVPARQPT ISLLCEDTAD TLSVESLTLV PPVDPHSLRS
LTGMPPLSTP AAACTEPVGE EAACAEPVGT AED
