CYTIP_HUMAN
ID CYTIP_HUMAN Reviewed; 359 AA.
AC O60759; B4DWH9; Q15630; Q8NE32;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Cytohesin-interacting protein;
DE AltName: Full=Cytohesin binder and regulator;
DE Short=CYBR;
DE AltName: Full=Cytohesin-associated scaffolding protein;
DE Short=CASP;
DE AltName: Full=Cytohesin-binding protein HE;
DE Short=Cbp HE;
DE AltName: Full=Pleckstrin homology Sec7 and coiled-coil domains-binding protein;
GN Name=CYTIP; Synonyms=PSCDBP;
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), TISSUE SPECIFICITY, DOMAIN, AND
RP INTERACTION WITH CYTH1.
RX PubMed=11867758; DOI=10.1073/pnas.052712999;
RA Tang P., Cheng T.P., Agnello D., Wu C.-Y., Hissong B.D., Watford W.T.,
RA Ahn H.-J., Galon J., Moss J., Vaughan M., O'Shea J.J., Gadina M.;
RT "Cybr, a cytokine-inducible protein that binds cytohesin-1 and regulates
RT its activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:2625-2629(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, INDUCTION,
RP DOMAIN, TISSUE SPECIFICITY, INTERACTION WITH CYTH1, AND MUTAGENESIS OF
RP LYS-82; PHE-90 AND ILE-92.
RX PubMed=12606567; DOI=10.1093/emboj/cdg101;
RA Boehm T., Hofer S., Winklehner P., Kellersch B., Geiger C.,
RA Trockenbacher A., Neyer S., Fiegl H., Ebner S., Ivarsson L., Schneider R.,
RA Kremmer E., Heufler C., Kolanus W.;
RT "Attenuation of cell adhesion in lymphocytes is regulated by CYTIP, a
RT protein which mediates signal complex sequestration.";
RL EMBO J. 22:1014-1024(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary gland;
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 GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-359 (ISOFORM 1), AND VARIANT ASN-37.
RC TISSUE=Blood;
RX PubMed=8241278; DOI=10.1016/0167-4781(93)90165-a;
RA Dixon B., Sahely B., Liu L., Pohajdak B.;
RT "Cloning a cDNA from human NK/T cells which codes for an unusual leucine
RT zipper containing protein.";
RL Biochim. Biophys. Acta 1216:321-324(1993).
RN [7]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SNX27.
RX PubMed=17577583; DOI=10.1016/j.bbrc.2007.05.162;
RA MacNeil A.J., Mansour M., Pohajdak B.;
RT "Sorting nexin 27 interacts with the Cytohesin associated scaffolding
RT protein (CASP) in lymphocytes.";
RL Biochem. Biophys. Res. Commun. 359:848-853(2007).
RN [8]
RP VARIANT SER-329.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
CC -!- FUNCTION: By its binding to cytohesin-1 (CYTH1), it modifies activation
CC of ARFs by CYTH1 and its precise function may be to sequester CYTH1 in
CC the cytoplasm.
CC -!- SUBUNIT: Interacts with CYTH1 and SNX27. {ECO:0000269|PubMed:11867758,
CC ECO:0000269|PubMed:12606567, ECO:0000269|PubMed:17577583}.
CC -!- INTERACTION:
CC O60759; Q15438: CYTH1; NbExp=6; IntAct=EBI-997814, EBI-997830;
CC O60759; P22607: FGFR3; NbExp=3; IntAct=EBI-997814, EBI-348399;
CC O60759; Q9HAQ2: KIF9; NbExp=3; IntAct=EBI-997814, EBI-8472129;
CC O60759; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-997814, EBI-348259;
CC O60759; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-997814, EBI-748391;
CC O60759; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-997814, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Early endosome. Note=Recruited from
CC the cytosol to endosomes by SNX27.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60759-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60759-2; Sequence=VSP_055502;
CC -!- TISSUE SPECIFICITY: Expressed in lymph nodes, thymus, spleen, lung,
CC peripheral blood leukocytes and bone marrow.
CC {ECO:0000269|PubMed:11867758, ECO:0000269|PubMed:12606567}.
CC -!- INDUCTION: By TNF and bacterial lipopolysaccharides (LPS).
CC {ECO:0000269|PubMed:12606567}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA16575.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF068836; AAC19129.1; -; mRNA.
DR EMBL; AK301544; BAG63041.1; -; mRNA.
DR EMBL; AC019201; AAY14898.1; -; Genomic_DNA.
DR EMBL; BC036449; AAH36449.1; -; mRNA.
DR EMBL; L06633; AAA16575.1; ALT_INIT; mRNA.
DR CCDS; CCDS2204.1; -. [O60759-1]
DR PIR; S43424; S43424.
DR RefSeq; NP_004279.3; NM_004288.4. [O60759-1]
DR RefSeq; XP_016860875.1; XM_017005386.1. [O60759-2]
DR PDB; 2Z17; X-ray; 2.70 A; A=67-163.
DR PDBsum; 2Z17; -.
DR AlphaFoldDB; O60759; -.
DR SMR; O60759; -.
DR BioGRID; 114961; 16.
DR IntAct; O60759; 16.
DR MINT; O60759; -.
DR STRING; 9606.ENSP00000264192; -.
DR iPTMnet; O60759; -.
DR PhosphoSitePlus; O60759; -.
DR BioMuta; CYTIP; -.
DR jPOST; O60759; -.
DR MassIVE; O60759; -.
DR MaxQB; O60759; -.
DR PaxDb; O60759; -.
DR PeptideAtlas; O60759; -.
DR PRIDE; O60759; -.
DR ProteomicsDB; 49587; -. [O60759-1]
DR ProteomicsDB; 5340; -.
DR Antibodypedia; 1992; 138 antibodies from 31 providers.
DR DNASU; 9595; -.
DR Ensembl; ENST00000264192.8; ENSP00000264192.3; ENSG00000115165.10. [O60759-1]
DR GeneID; 9595; -.
DR KEGG; hsa:9595; -.
DR MANE-Select; ENST00000264192.8; ENSP00000264192.3; NM_004288.5; NP_004279.3.
DR UCSC; uc002tzj.2; human. [O60759-1]
DR CTD; 9595; -.
DR DisGeNET; 9595; -.
DR GeneCards; CYTIP; -.
DR HGNC; HGNC:9506; CYTIP.
DR HPA; ENSG00000115165; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 604448; gene.
DR neXtProt; NX_O60759; -.
DR OpenTargets; ENSG00000115165; -.
DR PharmGKB; PA164718652; -.
DR VEuPathDB; HostDB:ENSG00000115165; -.
DR eggNOG; KOG3528; Eukaryota.
DR GeneTree; ENSGT00530000063734; -.
DR HOGENOM; CLU_058640_1_0_1; -.
DR InParanoid; O60759; -.
DR OMA; WLSSMTV; -.
DR OrthoDB; 966869at2759; -.
DR PhylomeDB; O60759; -.
DR TreeFam; TF316315; -.
DR PathwayCommons; O60759; -.
DR SignaLink; O60759; -.
DR BioGRID-ORCS; 9595; 11 hits in 1068 CRISPR screens.
DR ChiTaRS; CYTIP; human.
DR EvolutionaryTrace; O60759; -.
DR GeneWiki; PSCDBP; -.
DR GenomeRNAi; 9595; -.
DR Pharos; O60759; Tbio.
DR PRO; PR:O60759; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O60759; protein.
DR Bgee; ENSG00000115165; Expressed in blood and 163 other tissues.
DR ExpressionAtlas; O60759; baseline and differential.
DR Genevisible; O60759; HS.
DR GO; GO:0005938; C:cell cortex; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0030155; P:regulation of cell adhesion; IDA:MGI.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR Pfam; PF00595; PDZ; 1.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS50106; PDZ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; Endosome;
KW Reference proteome.
FT CHAIN 1..359
FT /note="Cytohesin-interacting protein"
FT /id="PRO_0000097061"
FT DOMAIN 77..166
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 166..188
FT /note="Interaction with CYTH1"
FT COILED 166..188
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..106
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055502"
FT VARIANT 37
FT /note="D -> N (in dbSNP:rs1042038)"
FT /evidence="ECO:0000269|PubMed:8241278"
FT /id="VAR_023534"
FT VARIANT 83
FT /note="Q -> E (in dbSNP:rs2229345)"
FT /id="VAR_051287"
FT VARIANT 329
FT /note="P -> S (found in a renal cell carcinoma case;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064706"
FT MUTAGEN 82
FT /note="K->E: No membrane-association. No change in the
FT binding to CYTH1; when associated with A-90 and A-92."
FT /evidence="ECO:0000269|PubMed:12606567"
FT MUTAGEN 90
FT /note="F->A: No membrane-association. No change in the
FT binding to CYTH1; when associated with E-82 and A-92."
FT /evidence="ECO:0000269|PubMed:12606567"
FT MUTAGEN 92
FT /note="I->A: No membrane-association. No change in the
FT binding to CYTH1; when associated with E-82 and A-90."
FT /evidence="ECO:0000269|PubMed:12606567"
FT CONFLICT 278
FT /note="T -> Q (in Ref. 6; AAA16575)"
FT /evidence="ECO:0000305"
FT CONFLICT 339..341
FT /note="KQL -> RVA (in Ref. 6; AAA16575)"
FT /evidence="ECO:0000305"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:2Z17"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:2Z17"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:2Z17"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:2Z17"
FT HELIX 119..123
FT /evidence="ECO:0007829|PDB:2Z17"
FT HELIX 144..153
FT /evidence="ECO:0007829|PDB:2Z17"
FT TURN 154..156
FT /evidence="ECO:0007829|PDB:2Z17"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:2Z17"
SQ SEQUENCE 359 AA; 40010 MW; 76F0E0ED02EDD8C2 CRC64;
MSLQRLLQHS SNGNLADFCA GPAYSSYSTL TGSLTMDDNR RIQMLADTVA TLPRGRKQLA
LTRSSSLSDF SWSQRKLVTV EKQDNETFGF EIQSYRPQNQ NACSSEMFTL ICKIQEDSPA
HCAGLQAGDV LANINGVSTE GFTYKQVVDL IRSSGNLLTI ETLNGTMILK RTELEAKLQV
LKQTLKQKWV EYRSLQLQEH RLLHGDAANC PSLENMDLDE LSLFGPLPGP GPALVDRNRL
SSESSCKSWL SSMTMDSEDG YQTCVSEDSS RGAFSRQTST DDECFIPKEG DDFLRRSSSR
RNRSISNTSS GSMSPLWEGN LSSMFGTLPR KSRKGSVRKQ LLKFIPGLHR AVEEEESRF
