ICA69_HUMAN
ID ICA69_HUMAN Reviewed; 483 AA.
AC Q05084; A8K7U1; B3FTQ2; P78506; Q13824; Q96HG3;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Islet cell autoantigen 1;
DE AltName: Full=69 kDa islet cell autoantigen;
DE Short=ICA69;
DE AltName: Full=Islet cell autoantigen p69;
DE Short=ICAp69;
DE Short=p69;
GN Name=ICA1;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=8326004; DOI=10.1172/jci116574;
RA Pietropaolo M., Castano L., Babu S., Buelow R., Kuo Y.-L.S., Martin S.,
RA Martin A., Powers A.C., Prochazka M., Naggert J., Leiter E.H.,
RA Eisenbarth G.S.;
RT "Islet cell autoantigen 69 kD (ICA69). Molecular cloning and
RT characterization of a novel diabetes-associated autoantigen.";
RL J. Clin. Invest. 92:359-371(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Pancreatic islet;
RX PubMed=7918678; DOI=10.1016/0925-4439(94)90113-9;
RA Miyazaki I., Gaedigk R., Hui M.F., Cheung R.K., Morkowski J., Rajotte R.V.,
RA Dosch H.-M.;
RT "Cloning of human and rat p69 cDNA, a candidate autoimmune target in type 1
RT diabetes.";
RL Biochim. Biophys. Acta 1227:101-104(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8975715; DOI=10.1006/geno.1996.0641;
RA Gaedigk R., Karges W., Hui M.F., Scherer S.W., Dosch H.-M.;
RT "Genomic organization and transcript analysis of ICAp69, a target antigen
RT in diabetic autoimmunity.";
RL Genomics 38:382-391(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Hoehne M., Lorscheider J., Schermer B., Benzing T.;
RT "A new transcript variant of human ICA69.";
RL Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovium;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [7]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 [9]
RP SUBCELLULAR LOCATION.
RX PubMed=12682071; DOI=10.1074/jbc.m213222200;
RA Spitzenberger F., Pietropaolo S., Verkade P., Habermann B.,
RA Lacas-Gervais S., Mziaut H., Pietropaolo M., Solimena M.;
RT "Islet cell autoantigen of 69 kDa is an arfaptin-related protein associated
RT with the Golgi complex of insulinoma INS-1 cells.";
RL J. Biol. Chem. 278:26166-26173(2003).
CC -!- FUNCTION: May play a role in neurotransmitter secretion. {ECO:0000250}.
CC -!- INTERACTION:
CC Q05084; Q7Z6N9: CCDC28A; NbExp=3; IntAct=EBI-1046751, EBI-10258115;
CC Q05084; Q8IWP9: CCDC28A; NbExp=3; IntAct=EBI-1046751, EBI-355471;
CC Q05084; Q8WYH8: ING5; NbExp=3; IntAct=EBI-1046751, EBI-488533;
CC Q05084; O95983: MBD3; NbExp=3; IntAct=EBI-1046751, EBI-1783068;
CC Q05084; P61019: RAB2A; NbExp=4; IntAct=EBI-1046751, EBI-752037;
CC Q05084; Q8WUD1: RAB2B; NbExp=4; IntAct=EBI-1046751, EBI-5542466;
CC Q05084-3; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-25930511, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12682071}.
CC Golgi apparatus membrane {ECO:0000305}; Peripheral membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Cytoplasmic
CC vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000305};
CC Peripheral membrane protein {ECO:0000305}. Note=Predominantly
CC cytosolic. Also exists as a membrane-bound form which has been found
CC associated with synaptic vesicles and also with the Golgi complex and
CC immature secretory granules.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q05084-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q05084-2; Sequence=VSP_047761;
CC Name=3;
CC IsoId=Q05084-3; Sequence=VSP_055405;
CC -!- TISSUE SPECIFICITY: Expressed abundantly in pancreas, heart and brain
CC with low levels of expression in lung, kidney, liver and thyroid.
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DR EMBL; L01100; AAA02564.1; -; mRNA.
DR EMBL; L21181; AAA64927.1; -; mRNA.
DR EMBL; U26591; AAB19033.1; -; mRNA.
DR EMBL; U37183; AAC50935.1; -; mRNA.
DR EMBL; U71264; AAB94738.1; -; Genomic_DNA.
DR EMBL; U71251; AAB94738.1; JOINED; Genomic_DNA.
DR EMBL; U71252; AAB94738.1; JOINED; Genomic_DNA.
DR EMBL; U71253; AAB94738.1; JOINED; Genomic_DNA.
DR EMBL; U71255; AAB94738.1; JOINED; Genomic_DNA.
DR EMBL; U71256; AAB94738.1; JOINED; Genomic_DNA.
DR EMBL; U71257; AAB94738.1; JOINED; Genomic_DNA.
DR EMBL; U71258; AAB94738.1; JOINED; Genomic_DNA.
DR EMBL; U71259; AAB94738.1; JOINED; Genomic_DNA.
DR EMBL; U71260; AAB94738.1; JOINED; Genomic_DNA.
DR EMBL; U71261; AAB94738.1; JOINED; Genomic_DNA.
DR EMBL; U71262; AAB94738.1; JOINED; Genomic_DNA.
DR EMBL; U71263; AAB94738.1; JOINED; Genomic_DNA.
DR EMBL; EU416199; ACB47390.1; -; mRNA.
DR EMBL; AK292106; BAF84795.1; -; mRNA.
DR EMBL; AC006042; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC007009; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471073; EAW93610.1; -; Genomic_DNA.
DR EMBL; CH471073; EAW93617.1; -; Genomic_DNA.
DR EMBL; BC008640; AAH08640.1; -; mRNA.
DR CCDS; CCDS34602.1; -. [Q05084-1]
DR CCDS; CCDS64595.1; -. [Q05084-3]
DR CCDS; CCDS87478.1; -. [Q05084-2]
DR PIR; I55598; I55598.
DR RefSeq; NP_001129492.1; NM_001136020.2. [Q05084-1]
DR RefSeq; NP_001263407.1; NM_001276478.1. [Q05084-3]
DR RefSeq; NP_004959.2; NM_004968.3. [Q05084-1]
DR RefSeq; NP_071682.1; NM_022307.2. [Q05084-1]
DR RefSeq; XP_005249792.1; XM_005249735.3.
DR RefSeq; XP_011513647.1; XM_011515345.1.
DR RefSeq; XP_011513648.1; XM_011515346.1.
DR RefSeq; XP_011513649.1; XM_011515347.2. [Q05084-2]
DR RefSeq; XP_011513650.1; XM_011515348.1. [Q05084-2]
DR RefSeq; XP_011513651.1; XM_011515349.1. [Q05084-2]
DR RefSeq; XP_016867606.1; XM_017012117.1.
DR RefSeq; XP_016867607.1; XM_017012118.1.
DR RefSeq; XP_016867608.1; XM_017012119.1.
DR RefSeq; XP_016867609.1; XM_017012120.1.
DR RefSeq; XP_016867610.1; XM_017012121.1.
DR AlphaFoldDB; Q05084; -.
DR BioGRID; 109609; 24.
DR IntAct; Q05084; 13.
DR MINT; Q05084; -.
DR STRING; 9606.ENSP00000385570; -.
DR iPTMnet; Q05084; -.
DR PhosphoSitePlus; Q05084; -.
DR BioMuta; ICA1; -.
DR DMDM; 20141584; -.
DR EPD; Q05084; -.
DR jPOST; Q05084; -.
DR MassIVE; Q05084; -.
DR MaxQB; Q05084; -.
DR PaxDb; Q05084; -.
DR PeptideAtlas; Q05084; -.
DR PRIDE; Q05084; -.
DR ProteomicsDB; 3477; -.
DR ProteomicsDB; 58305; -. [Q05084-1]
DR ProteomicsDB; 76745; -.
DR Antibodypedia; 1895; 258 antibodies from 27 providers.
DR DNASU; 3382; -.
DR Ensembl; ENST00000265577.11; ENSP00000265577.7; ENSG00000003147.19. [Q05084-3]
DR Ensembl; ENST00000396675.7; ENSP00000379908.3; ENSG00000003147.19. [Q05084-1]
DR Ensembl; ENST00000402384.8; ENSP00000385570.3; ENSG00000003147.19. [Q05084-1]
DR Ensembl; ENST00000406470.6; ENSP00000385651.2; ENSG00000003147.19. [Q05084-1]
DR Ensembl; ENST00000422063.6; ENSP00000403982.2; ENSG00000003147.19. [Q05084-2]
DR GeneID; 3382; -.
DR KEGG; hsa:3382; -.
DR MANE-Select; ENST00000402384.8; ENSP00000385570.3; NM_001136020.3; NP_001129492.1.
DR UCSC; uc003srm.4; human. [Q05084-1]
DR CTD; 3382; -.
DR DisGeNET; 3382; -.
DR GeneCards; ICA1; -.
DR HGNC; HGNC:5343; ICA1.
DR HPA; ENSG00000003147; Low tissue specificity.
DR MIM; 147625; gene.
DR neXtProt; NX_Q05084; -.
DR OpenTargets; ENSG00000003147; -.
DR PharmGKB; PA29591; -.
DR VEuPathDB; HostDB:ENSG00000003147; -.
DR eggNOG; KOG3891; Eukaryota.
DR GeneTree; ENSGT00390000005530; -.
DR InParanoid; Q05084; -.
DR OMA; THNACSE; -.
DR OrthoDB; 766523at2759; -.
DR PhylomeDB; Q05084; -.
DR TreeFam; TF317186; -.
DR PathwayCommons; Q05084; -.
DR SignaLink; Q05084; -.
DR BioGRID-ORCS; 3382; 10 hits in 1082 CRISPR screens.
DR ChiTaRS; ICA1; human.
DR GeneWiki; ICA1; -.
DR GenomeRNAi; 3382; -.
DR Pharos; Q05084; Tbio.
DR PRO; PR:Q05084; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q05084; protein.
DR Bgee; ENSG00000003147; Expressed in body of pancreas and 181 other tissues.
DR ExpressionAtlas; Q05084; baseline and differential.
DR Genevisible; Q05084; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0030667; C:secretory granule membrane; IDA:UniProtKB.
DR GO; GO:0030672; C:synaptic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0140090; F:membrane curvature sensor activity; IDA:FlyBase.
DR GO; GO:0019904; F:protein domain specific binding; IEA:InterPro.
DR GO; GO:0006836; P:neurotransmitter transport; IEA:UniProtKB-KW.
DR GO; GO:0050796; P:regulation of insulin secretion; IEA:InterPro.
DR GO; GO:0051049; P:regulation of transport; IBA:GO_Central.
DR Gene3D; 1.20.1270.60; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR010504; AH_dom.
DR InterPro; IPR030796; ICA1.
DR InterPro; IPR024114; Islet_autoAg_Ica1/Ica1-like.
DR InterPro; IPR006723; Islet_autoAg_Ica1_C.
DR PANTHER; PTHR10164; PTHR10164; 1.
DR PANTHER; PTHR10164:SF3; PTHR10164:SF3; 1.
DR Pfam; PF06456; Arfaptin; 1.
DR Pfam; PF04629; ICA69; 2.
DR SMART; SM01015; Arfaptin; 1.
DR SMART; SM01237; ICA69; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR PROSITE; PS50870; AH; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Cytoplasmic vesicle; Golgi apparatus;
KW Membrane; Neurotransmitter transport; Reference proteome; Synapse;
KW Transport.
FT CHAIN 1..483
FT /note="Islet cell autoantigen 1"
FT /id="PRO_0000084130"
FT DOMAIN 51..254
FT /note="AH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00294"
FT REGION 281..321
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 290..304
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 305..319
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 7
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055405"
FT VAR_SEQ 301
FT /note="Q -> QYLQNICLEMKANSDIKMLQKGKEGQQIGI (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047761"
FT CONFLICT 29
FT /note="K -> R (in Ref. 1; AAA02564)"
FT /evidence="ECO:0000305"
FT CONFLICT 83
FT /note="R -> G (in Ref. 2; AAA64927)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 483 AA; 54645 MW; 1696F928EE7454C9 CRC64;
MSGHKCSYPW DLQDRYAQDK SVVNKMQQKY WETKQAFIKA TGKKEDEHVV ASDADLDAKL
ELFHSIQRTC LDLSKAIVLY QKRICFLSQE ENELGKFLRS QGFQDKTRAG KMMQATGKAL
CFSSQQRLAL RNPLCRFHQE VETFRHRAIS DTWLTVNRME QCRTEYRGAL LWMKDVSQEL
DPDLYKQMEK FRKVQTQVRL AKKNFDKLKM DVCQKVDLLG ASRCNLLSHM LATYQTTLLH
FWEKTSHTMA AIHESFKGYQ PYEFTTLKSL QDPMKKLVEK EEKKKINQQE STDAAVQEPS
QLISLEEENQ RKESSSFKTE DGKSILSALD KGSTHTACSG PIDELLDMKS EEGACLGPVA
GTPEPEGADK DDLLLLSEIF NASSLEEGEF SKEWAAVFGD GQVKEPVPTM ALGEPDPKAQ
TGSGFLPSQL LDQNMKDLQA SLQEPAKAAS DLTAWFSLFA DLDPLSNPDA VGKTDKEHEL
LNA
