CARF_HUMAN
ID CARF_HUMAN Reviewed; 580 AA.
AC Q9NXV6; Q8TBM5; Q9NYH0;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 3.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=CDKN2A-interacting protein;
DE AltName: Full=Collaborator of ARF;
GN Name=CDKN2AIP; Synonyms=CARF;
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], INTERACTION WITH CDKN2A, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12154087; DOI=10.1074/jbc.m204177200;
RA Hasan M.K., Yaguchi T., Sugihara T., Kumar P.K.R., Taira K., Reddel R.R.,
RA Kaul S.C., Wadhwa R.;
RT "CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF)
RT in activating p53.";
RL J. Biol. Chem. 277:37765-37770(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [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].
RC TISSUE=Testis;
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 PROTEIN SEQUENCE OF 2-14; 42-68; 129-142 AND 209-229, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Dozynkiewicz M., Norman J.C.;
RL Submitted (JUN-2009) to UniProtKB.
RN [6]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH CDKN2A.
RX PubMed=12581788; DOI=10.1016/s0531-5565(02)00180-8;
RA Wadhwa R., Sugihara T., Hasan M.K., Duncan E.L., Taira K., Kaul S.C.;
RT "A novel putative collaborator of p19ARF.";
RL Exp. Gerontol. 38:245-252(2003).
RN [7]
RP INTERACTION WITH TP53, AND FUNCTION.
RX PubMed=15109303; DOI=10.1042/bj20040337;
RA Hasan M.K., Yaguchi T., Minoda Y., Hirano T., Taira K., Wadhwa R.,
RA Kaul S.C.;
RT "Alternative reading frame protein (ARF)-independent function of CARF
RT (collaborator of ARF) involves its interactions with p53: evidence for a
RT novel p53-activation pathway and its negative feedback control.";
RL Biochem. J. 380:605-610(2004).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-346, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP INTERACTION WITH MDM2.
RX PubMed=17460193; DOI=10.1196/annals.1395.033;
RA Kamrul H.M., Wadhwa R., Kaul S.C.;
RT "CARF binds to three members (ARF, p53, and HDM2) of the p53 tumor-
RT suppressor pathway.";
RL Ann. N. Y. Acad. Sci. 1100:312-315(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-346, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131; THR-346 AND SER-389, AND
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 [15]
RP INDUCTION.
RX PubMed=24485912; DOI=10.1016/j.yexcr.2014.01.022;
RA Singh R., Kalra R.S., Hasan K., Kaul Z., Cheung C.T., Huschtscha L.,
RA Reddel R.R., Kaul S.C., Wadhwa R.;
RT "Molecular characterization of collaborator of ARF (CARF) as a DNA damage
RT response and cell cycle checkpoint regulatory protein.";
RL Exp. Cell Res. 322:324-334(2014).
RN [16]
RP FUNCTION, AND INTERACTION WITH CHEK2 AND MAPK3.
RX PubMed=24825908; DOI=10.1074/jbc.m114.547208;
RA Cheung C.T., Singh R., Kalra R.S., Kaul S.C., Wadhwa R.;
RT "Collaborator of ARF (CARF) regulates proliferative fate of human cells by
RT dose-dependent regulation of DNA damage signaling.";
RL J. Biol. Chem. 289:18258-18269(2014).
RN [17]
RP IDENTIFICATION BY 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).
RN [18]
RP INTERACTION WITH XRN2.
RX PubMed=24462208; DOI=10.1016/j.molcel.2014.01.001;
RA Miki T.S., Richter H., Rueegger S., Grosshans H.;
RT "PAXT-1 promotes XRN2 activity by stabilizing it through a conserved
RT domain.";
RL Mol. Cell 53:351-360(2014).
RN [19]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-184, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
CC -!- FUNCTION: Regulates DNA damage response in a dose-dependent manner
CC through a number of signaling pathways involved in cell proliferation,
CC apoptosis and senescence. {ECO:0000269|PubMed:15109303,
CC ECO:0000269|PubMed:24825908}.
CC -!- SUBUNIT: Interacts with CDKN2A/p14ARF, p53/TP53 and MDM2. Interacts
CC with CHEK2 and MAPK3. Interacts with XRN2 (PubMed:24462208).
CC {ECO:0000269|PubMed:12154087, ECO:0000269|PubMed:12581788,
CC ECO:0000269|PubMed:15109303, ECO:0000269|PubMed:17460193,
CC ECO:0000269|PubMed:24462208, ECO:0000269|PubMed:24825908}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:12154087, ECO:0000269|PubMed:12581788}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:12581788}.
CC -!- INDUCTION: Up-regulated during replicative senescence, in response to
CC DNA-damaging drugs, telomere unprotection and oncogenic Ras-induced
CC stress. Induced by proteasomal inhibitor MG132. Up-regulated at G1 and
CC G2 stages of cell cycle. {ECO:0000269|PubMed:24485912}.
CC -!- PTM: May be ubiquitinated.
CC -!- SIMILARITY: Belongs to the CARF family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF68967.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF246705; AAF68967.1; ALT_FRAME; mRNA.
DR EMBL; AK000043; BAA90902.1; -; mRNA.
DR EMBL; CH471056; EAX04691.1; -; Genomic_DNA.
DR EMBL; BC022270; AAH22270.1; -; mRNA.
DR CCDS; CCDS34110.1; -.
DR RefSeq; NP_001304272.1; NM_001317343.1.
DR RefSeq; NP_060102.1; NM_017632.3.
DR AlphaFoldDB; Q9NXV6; -.
DR SMR; Q9NXV6; -.
DR BioGRID; 120743; 124.
DR DIP; DIP-24170N; -.
DR IntAct; Q9NXV6; 43.
DR MINT; Q9NXV6; -.
DR STRING; 9606.ENSP00000427108; -.
DR GlyConnect; 2902; 1 O-Linked glycan (3 sites).
DR GlyGen; Q9NXV6; 22 sites, 2 O-linked glycans (22 sites).
DR iPTMnet; Q9NXV6; -.
DR PhosphoSitePlus; Q9NXV6; -.
DR BioMuta; CDKN2AIP; -.
DR DMDM; 327478591; -.
DR EPD; Q9NXV6; -.
DR jPOST; Q9NXV6; -.
DR MassIVE; Q9NXV6; -.
DR MaxQB; Q9NXV6; -.
DR PaxDb; Q9NXV6; -.
DR PeptideAtlas; Q9NXV6; -.
DR PRIDE; Q9NXV6; -.
DR ProteomicsDB; 83138; -.
DR Antibodypedia; 17295; 227 antibodies from 32 providers.
DR DNASU; 55602; -.
DR Ensembl; ENST00000504169.2; ENSP00000427108.1; ENSG00000168564.6.
DR GeneID; 55602; -.
DR KEGG; hsa:55602; -.
DR MANE-Select; ENST00000504169.2; ENSP00000427108.1; NM_017632.4; NP_060102.1.
DR UCSC; uc003ivp.2; human.
DR CTD; 55602; -.
DR DisGeNET; 55602; -.
DR GeneCards; CDKN2AIP; -.
DR HGNC; HGNC:24325; CDKN2AIP.
DR HPA; ENSG00000168564; Low tissue specificity.
DR MIM; 615914; gene.
DR neXtProt; NX_Q9NXV6; -.
DR OpenTargets; ENSG00000168564; -.
DR PharmGKB; PA162382149; -.
DR VEuPathDB; HostDB:ENSG00000168564; -.
DR eggNOG; ENOG502S4FT; Eukaryota.
DR GeneTree; ENSGT00940000158376; -.
DR HOGENOM; CLU_019689_0_0_1; -.
DR InParanoid; Q9NXV6; -.
DR OMA; CRYPPQV; -.
DR OrthoDB; 1524198at2759; -.
DR PhylomeDB; Q9NXV6; -.
DR TreeFam; TF333807; -.
DR PathwayCommons; Q9NXV6; -.
DR SignaLink; Q9NXV6; -.
DR SIGNOR; Q9NXV6; -.
DR BioGRID-ORCS; 55602; 44 hits in 1083 CRISPR screens.
DR ChiTaRS; CDKN2AIP; human.
DR GenomeRNAi; 55602; -.
DR Pharos; Q9NXV6; Tbio.
DR PRO; PR:Q9NXV6; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9NXV6; protein.
DR Bgee; ENSG00000168564; Expressed in amniotic fluid and 188 other tissues.
DR ExpressionAtlas; Q9NXV6; baseline and differential.
DR Genevisible; Q9NXV6; HS.
DR GO; GO:0001652; C:granular component; IDA:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:BHF-UCL.
DR GO; GO:0002039; F:p53 binding; IDA:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:BHF-UCL.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0009967; P:positive regulation of signal transduction; IMP:BHF-UCL.
DR GO; GO:0031647; P:regulation of protein stability; IMP:BHF-UCL.
DR InterPro; IPR014720; dsRBD_dom.
DR InterPro; IPR021859; XTBD.
DR Pfam; PF11952; XTBD; 1.
DR PROSITE; PS50137; DS_RBD; 1.
DR PROSITE; PS51827; XTBD; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; RNA-binding; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PubMed:22814378"
FT CHAIN 2..580
FT /note="CDKN2A-interacting protein"
FT /id="PRO_0000324339"
FT DOMAIN 19..133
FT /note="XRN2-binding (XTBD)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01171"
FT DOMAIN 462..537
FT /note="DRBM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT REGION 129..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 129..164
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 165..228
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 244..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..356
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PubMed:22814378"
FT MOD_RES 131
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BI72"
FT MOD_RES 346
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 184
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CONFLICT 242
FT /note="Missing (in Ref. 3; EAX04691 and 4; AAH22270)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 580 AA; 61125 MW; 5CFCB5DFEE50A475 CRC64;
MAQEVSEYLS QNPRVAAWVE ALRCDGETDK HWRHRRDFLL RNAGDLAPAG GAASASTDEA
ADAESGTRNR QLQQLISFSM AWANHVFLGC RYPQKVMDKI LSMAEGIKVT DAPTYTTRDE
LVAKVKKRGI SSSNEGVEEP SKKRVIEGKN SSAVEQDHAK TSAKTERASA QQENSSTCIG
SAIKSESGNS ARSSGISSQN SSTSDGDRSV SSQSSSSVSS QVTTAGSGKA SEAEAPDKHG
SASFVSLLKS SVNSHMTQST DSRQQSGSPK KSALEGSSAS ASQSSSEIEV PLLGSSGSSE
VELPLLSSKP SSETASSGLT SKTSSEASVS SSVAKNSSSS GTSLLTPKSS SSTNTSLLTS
KSTSQVAASL LASKSSSQTS GSLVSKSTSL ASVSQLASKS SSQTSTSQLP SKSTSQSSES
SVKFSCKLTN EDVKQKQPFF NRLYKTVAWK LVAVGGFSPN VNHGELLNAA IEALKATLDV
FFVPLKELAD LPQNKSSQES IVCELRCKSV YLGTGCGKSK ENAKAVASRE ALKLFLKKKV
VVKICKRKYR GSEIEDLVLL DEESRPVNLP PALKHPQELL
