CGRE1_HUMAN
ID CGRE1_HUMAN Reviewed; 318 AA.
AC Q99674; A6NHV7; B4DXY8; B5MCB7; B5MCC9; B5MCP5; E7EU99; Q8N4B7;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 3.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Cell growth regulator with EF hand domain protein 1 {ECO:0000305};
DE AltName: Full=Cell growth regulatory gene 11 protein;
DE AltName: Full=Hydrophobestin;
DE Flags: Precursor;
GN Name=CGREF1 {ECO:0000312|HGNC:HGNC:16962};
GN Synonyms=CGR11 {ECO:0000303|PubMed:8968090};
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 4), VARIANTS GLU-243 AND
RP 253-ALA--GLU-269 DEL, AND INDUCTION BY TP53.
RC TISSUE=Fetal brain;
RX PubMed=8968090;
RA Madden S.L., Galella E.A., Riley D., Bertelsen A.H., Beaudry G.A.;
RT "Induction of cell growth regulatory genes by p53.";
RL Cancer Res. 56:5384-5390(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal brain;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND VARIANT
RP 253-ALA--GLU-269 DEL.
RC TISSUE=Testis, and Thalamus;
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 GENOMIC DNA], AND VARIANT 253-ALA--GLU-269
RP DEL.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANT
RP 253-ALA--GLU-269 DEL.
RC TISSUE=Brain;
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).
CC -!- FUNCTION: Mediates cell-cell adhesion in a calcium-dependent manner (By
CC similarity). Able to inhibit growth in several cell lines.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=4;
CC IsoId=Q99674-4; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99674-2; Sequence=VSP_060233, VSP_060234;
CC Name=3;
CC IsoId=Q99674-3; Sequence=VSP_060232, VSP_060235, VSP_060236;
CC -!- INDUCTION: By p53/TP53. {ECO:0000269|PubMed:8968090}.
CC -!- DOMAIN: Both EF-hands are required for function. {ECO:0000250}.
CC -!- PTM: Probably digested extracellularly by an unknown serine protease
CC generating extremely hydrophobic bioactive peptides. {ECO:0000250}.
CC -!- POLYMORPHISM: The number of repeats of 17 amino acids in the C-terminal
CC is polymorphic and varies between 3 and 4. The majority of available
CC transcripts lacks one of these repeats. The sequence shown,
CC corresponding to the reference genome (GRCh38/hg38), contains 4
CC repeats. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAX93168.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- SEQUENCE CAUTION: [Isoform 3]:
CC Sequence=BAG63550.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; U66468; AAC50896.1; -; mRNA.
DR EMBL; BX419588; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK290128; BAF82817.1; -; mRNA.
DR EMBL; AK302185; BAG63550.1; ALT_SEQ; mRNA.
DR EMBL; AC013403; AAX93168.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471053; EAX00637.1; -; Genomic_DNA.
DR EMBL; BC034764; AAH34764.1; -; mRNA.
DR CCDS; CCDS33162.2; -. [Q99674-4]
DR CCDS; CCDS54339.1; -. [Q99674-2]
DR RefSeq; NP_001159711.1; NM_001166239.1. [Q99674-4]
DR RefSeq; NP_001159712.1; NM_001166240.1. [Q99674-2]
DR RefSeq; NP_001288253.1; NM_001301324.1.
DR RefSeq; NP_006560.3; NM_006569.5. [Q99674-4]
DR AlphaFoldDB; Q99674; -.
DR SMR; Q99674; -.
DR BioGRID; 115911; 35.
DR IntAct; Q99674; 1.
DR STRING; 9606.ENSP00000385452; -.
DR GlyGen; Q99674; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q99674; -.
DR PhosphoSitePlus; Q99674; -.
DR BioMuta; CGREF1; -.
DR DMDM; 215273950; -.
DR EPD; Q99674; -.
DR jPOST; Q99674; -.
DR MassIVE; Q99674; -.
DR MaxQB; Q99674; -.
DR PeptideAtlas; Q99674; -.
DR PRIDE; Q99674; -.
DR ProteomicsDB; 18384; -.
DR ProteomicsDB; 6021; -.
DR ProteomicsDB; 6029; -.
DR ProteomicsDB; 6081; -.
DR Antibodypedia; 2192; 193 antibodies from 27 providers.
DR DNASU; 10669; -.
DR Ensembl; ENST00000312734.8; ENSP00000324025.4; ENSG00000138028.17. [Q99674-4]
DR Ensembl; ENST00000402394.6; ENSP00000385452.1; ENSG00000138028.17. [Q99674-4]
DR Ensembl; ENST00000402550.5; ENSP00000385103.1; ENSG00000138028.17. [Q99674-2]
DR Ensembl; ENST00000405600.5; ENSP00000386113.1; ENSG00000138028.17. [Q99674-4]
DR Ensembl; ENST00000640154.1; ENSP00000491464.1; ENSG00000138028.17. [Q99674-3]
DR GeneID; 10669; -.
DR KEGG; hsa:10669; -.
DR MANE-Select; ENST00000402394.6; ENSP00000385452.1; NM_006569.6; NP_006560.3.
DR UCSC; uc002riq.4; human. [Q99674-4]
DR CTD; 10669; -.
DR DisGeNET; 10669; -.
DR GeneCards; CGREF1; -.
DR HGNC; HGNC:16962; CGREF1.
DR HPA; ENSG00000138028; Tissue enhanced (brain, salivary gland).
DR MIM; 606137; gene.
DR neXtProt; NX_Q99674; -.
DR OpenTargets; ENSG00000138028; -.
DR PharmGKB; PA134984105; -.
DR VEuPathDB; HostDB:ENSG00000138028; -.
DR eggNOG; ENOG502S2TZ; Eukaryota.
DR GeneTree; ENSGT00940000154141; -.
DR HOGENOM; CLU_1916361_0_0_1; -.
DR InParanoid; Q99674; -.
DR OMA; MEKEPEH; -.
DR OrthoDB; 1308168at2759; -.
DR PhylomeDB; Q99674; -.
DR TreeFam; TF315801; -.
DR PathwayCommons; Q99674; -.
DR SignaLink; Q99674; -.
DR BioGRID-ORCS; 10669; 9 hits in 1081 CRISPR screens.
DR ChiTaRS; CGREF1; human.
DR GenomeRNAi; 10669; -.
DR Pharos; Q99674; Tbio.
DR PRO; PR:Q99674; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q99674; protein.
DR Bgee; ENSG00000138028; Expressed in right frontal lobe and 124 other tissues.
DR ExpressionAtlas; Q99674; baseline and differential.
DR Genevisible; Q99674; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
DR InterPro; IPR040139; CGREF1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR PANTHER; PTHR23104:SF11; PTHR23104:SF11; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 2: Evidence at transcript level;
KW Alternative splicing; Calcium; Cell adhesion; Cell cycle; Growth arrest;
KW Metal-binding; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..318
FT /note="Cell growth regulator with EF hand domain protein 1"
FT /id="PRO_0000073874"
FT DOMAIN 69..104
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 114..149
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REPEAT 219..235
FT /note="1"
FT REPEAT 236..252
FT /note="2"
FT REPEAT 253..269
FT /note="3"
FT REPEAT 270..286
FT /note="4; approximate"
FT REGION 177..318
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 219..286
FT /note="4 X 17 AA approximate tandem repeats of P-G-P-R-G-E-
FT A-G-G-Q-A-E-A-[KR]-G-D-A"
FT /evidence="ECO:0000303|PubMed:8968090"
FT COMPBIAS 183..203
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 280..295
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 82
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 84
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 86
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 88
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 93
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 129
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 131
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 138
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT VAR_SEQ 1..96
FT /note="Missing (in isoform 3)"
FT /id="VSP_060232"
FT VAR_SEQ 115..132
FT /note="VILIVDKVLETQDLNGDG -> GNLDARLDGGEKAMQPQW (in isoform
FT 2)"
FT /id="VSP_060233"
FT VAR_SEQ 133..318
FT /note="Missing (in isoform 2)"
FT /id="VSP_060234"
FT VAR_SEQ 149..208
FT /note="HVEPGEPLAPSPQEPQAVGRQSLLAKSPLRQETQEAPGPREEAKGQVEARRE
FT SLDPVQEP -> PYPPYIGVGPNSNMCSRSDLPEDSNTLYPGSHLWLRHALNSKGNLDA
FT RLDGGEKAMQPQW (in isoform 3)"
FT /id="VSP_060235"
FT VAR_SEQ 209..318
FT /note="Missing (in isoform 3)"
FT /id="VSP_060236"
FT VARIANT 116
FT /note="I -> M (in dbSNP:rs2384572)"
FT /id="VAR_061088"
FT VARIANT 212
FT /note="A -> V (in dbSNP:rs11893478)"
FT /id="VAR_047648"
FT VARIANT 226
FT /note="E -> G (in dbSNP:rs74360681)"
FT /id="VAR_081928"
FT VARIANT 232
FT /note="K -> E (in dbSNP:rs11889832)"
FT /id="VAR_081929"
FT VARIANT 232
FT /note="K -> N (in dbSNP:rs11889831)"
FT /id="VAR_047649"
FT VARIANT 243
FT /note="G -> E (in dbSNP:rs1057389)"
FT /evidence="ECO:0000269|PubMed:8968090"
FT /id="VAR_047650"
FT VARIANT 253..269
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:8968090,
FT ECO:0000269|Ref.5"
FT /id="VAR_081930"
FT CONFLICT 249
FT /note="E -> K (in Ref. 1; AAC50896)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 318 AA; 33456 MW; CA4BBDB696865CB6 CRC64;
MLPLTMTVLI LLLLPTGQAA PKDGVTRPDS EVQHQLLPNP FQPGQEQLGL LQSYLKGLGR
TEVQLEHLSR EQVLLYLFAL HDYDQSGQLD GLELLSMLTA ALAPGAANSP TTNPVILIVD
KVLETQDLNG DGLMTPAELI NFPGVALRHV EPGEPLAPSP QEPQAVGRQS LLAKSPLRQE
TQEAPGPREE AKGQVEARRE SLDPVQEPGG QAEADGDVPG PRGEAEGQAE AKGDAPGPRG
EAGGQAEAEG DAPGPRGEAG GQAEAEGDAP GPRGEAGGQA EARENGEEAK ELPGETLESK
NTQNDFEVHI VQVENDEI
