ID   CRIM1_HUMAN             Reviewed;        1036 AA.
AC   Q9NZV1; Q2M2G4; Q59GH0; Q7LCQ5; Q9H318;
DT   07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   27-MAR-2024, entry version 177.
DE   RecName: Full=Cysteine-rich motor neuron 1 protein;
DE            Short=CRIM-1;
DE   AltName: Full=Cysteine-rich repeat-containing protein S52;
DE   Contains:
DE     RecName: Full=Processed cysteine-rich motor neuron 1 protein;
DE   Flags: Precursor;
GN   Name=CRIM1; Synonyms=S52; ORFNames=UNQ1886/PRO4330;
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 [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=10642437; DOI=10.1016/s0925-4773(99)00248-8;
RA   Kolle G.V., Georgas K., Holmes G.P., Little M.H., Yamada T.;
RT   "CRIM1, a novel gene encoding a cysteine-rich repeat protein, is
RT   developmentally regulated and implicated in vertebrate CNS development and
RT   organogenesis.";
RL   Mech. Dev. 90:181-193(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA   Ohara O., Nagase T., Kikuno R.F.;
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
RN   [5]
RP   PROTEIN SEQUENCE OF 35-44, FUNCTION, GLYCOSYLATION, SUBCELLULAR LOCATION,
RP   INTERACTION WITH BMP4 AND BMP7, AND IDENTIFICATION OF A SOLUBLE FORM.
RX   PubMed=12805376; DOI=10.1074/jbc.m301247200;
RA   Wilkinson L., Kolle G.V., Wen D., Piper M., Scott J., Little M.H.;
RT   "CRIM1 regulates the rate of processing and delivery of bone morphogenetic
RT   proteins to the cell surface.";
RL   J. Biol. Chem. 278:34181-34188(2003).
RN   [6]
RP   PROTEIN SEQUENCE OF 35-49.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally verified
RT   cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [7]
RP   FUNCTION, GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX   PubMed=12464430; DOI=10.1016/s0925-4773(02)00355-6;
RA   Glienke J., Sturz A., Menrad A., Thierauch K.-H.;
RT   "CRIM1 is involved in endothelial cell capillary formation in vitro and is
RT   expressed in blood vessels in vivo.";
RL   Mech. Dev. 119:165-175(2002).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1035, 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   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1035, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
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).
CC   -!- FUNCTION: May play a role in CNS development by interacting with growth
CC       factors implicated in motor neuron differentiation and survival. May
CC       play a role in capillary formation and maintenance during angiogenesis.
CC       Modulates BMP activity by affecting its processing and delivery to the
CC       cell surface. {ECO:0000269|PubMed:12464430,
CC       ECO:0000269|PubMed:12805376}.
CC   -!- SUBUNIT: Interacts with BMP4 and BMP7. {ECO:0000269|PubMed:12805376}.
CC   -!- SUBCELLULAR LOCATION: [Processed cysteine-rich motor neuron 1 protein]:
CC       Secreted.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12805376};
CC       Single-pass type I membrane protein {ECO:0000269|PubMed:12805376}.
CC   -!- TISSUE SPECIFICITY: Expressed in pancreas, kidney, skeletal muscle,
CC       lung, placenta, brain, heart, spleen, liver and small intestine.
CC       Expressed in blood vessels (at protein level).
CC       {ECO:0000269|PubMed:10642437, ECO:0000269|PubMed:12464430}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12464430,
CC       ECO:0000269|PubMed:12805376}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAD92376.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AF167706; AAF34409.1; -; mRNA.
DR   EMBL; AF168681; AAG37011.1; -; Genomic_DNA.
DR   EMBL; AB209139; BAD92376.1; ALT_INIT; mRNA.
DR   EMBL; AY358371; AAQ88737.1; -; mRNA.
DR   EMBL; BC111989; AAI11990.1; -; mRNA.
DR   EMBL; BC113371; AAI13372.1; -; mRNA.
DR   CCDS; CCDS1783.1; -.
DR   RefSeq; NP_057525.1; NM_016441.2.
DR   AlphaFoldDB; Q9NZV1; -.
DR   SMR; Q9NZV1; -.
DR   BioGRID; 119395; 29.
DR   DIP; DIP-58932N; -.
DR   IntAct; Q9NZV1; 14.
DR   MINT; Q9NZV1; -.
DR   STRING; 9606.ENSP00000280527; -.
DR   TCDB; 9.B.87.1.36; the selenoprotein p receptor (selp-receptor) family.
DR   GlyCosmos; Q9NZV1; 7 sites, 2 glycans.
DR   GlyGen; Q9NZV1; 14 sites, 4 O-linked glycans (9 sites).
DR   iPTMnet; Q9NZV1; -.
DR   PhosphoSitePlus; Q9NZV1; -.
DR   SwissPalm; Q9NZV1; -.
DR   BioMuta; CRIM1; -.
DR   DMDM; 67460590; -.
DR   EPD; Q9NZV1; -.
DR   jPOST; Q9NZV1; -.
DR   MassIVE; Q9NZV1; -.
DR   MaxQB; Q9NZV1; -.
DR   PaxDb; 9606-ENSP00000280527; -.
DR   PeptideAtlas; Q9NZV1; -.
DR   ProteomicsDB; 83516; -.
DR   Pumba; Q9NZV1; -.
DR   Antibodypedia; 617; 196 antibodies from 28 providers.
DR   DNASU; 51232; -.
DR   Ensembl; ENST00000280527.7; ENSP00000280527.2; ENSG00000150938.10.
DR   GeneID; 51232; -.
DR   KEGG; hsa:51232; -.
DR   MANE-Select; ENST00000280527.7; ENSP00000280527.2; NM_016441.3; NP_057525.1.
DR   UCSC; uc002rpd.4; human.
DR   AGR; HGNC:2359; -.
DR   CTD; 51232; -.
DR   DisGeNET; 51232; -.
DR   GeneCards; CRIM1; -.
DR   HGNC; HGNC:2359; CRIM1.
DR   HPA; ENSG00000150938; Tissue enhanced (placenta).
DR   MalaCards; CRIM1; -.
DR   MIM; 606189; gene.
DR   neXtProt; NX_Q9NZV1; -.
DR   OpenTargets; ENSG00000150938; -.
DR   Orphanet; 468672; Colobomatous macrophthalmia-microcornea syndrome.
DR   PharmGKB; PA26877; -.
DR   VEuPathDB; HostDB:ENSG00000150938; -.
DR   eggNOG; KOG1216; Eukaryota.
DR   GeneTree; ENSGT00940000160910; -.
DR   HOGENOM; CLU_008434_0_0_1; -.
DR   InParanoid; Q9NZV1; -.
DR   OMA; FNNVEYH; -.
DR   OrthoDB; 2946817at2759; -.
DR   PhylomeDB; Q9NZV1; -.
DR   TreeFam; TF106451; -.
DR   PathwayCommons; Q9NZV1; -.
DR   SignaLink; Q9NZV1; -.
DR   BioGRID-ORCS; 51232; 5 hits in 1142 CRISPR screens.
DR   ChiTaRS; CRIM1; human.
DR   GeneWiki; CRIM1; -.
DR   GenomeRNAi; 51232; -.
DR   Pharos; Q9NZV1; Tbio.
DR   PRO; PR:Q9NZV1; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q9NZV1; Protein.
DR   Bgee; ENSG00000150938; Expressed in saphenous vein and 209 other cell types or tissues.
DR   ExpressionAtlas; Q9NZV1; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; TAS:ProtInc.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0005010; F:insulin-like growth factor receptor activity; TAS:ProtInc.
DR   GO; GO:0030165; F:PDZ domain binding; IDA:MGI.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:InterPro.
DR   GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:ARUK-UCL.
DR   GO; GO:0045668; P:negative regulation of osteoblast differentiation; IMP:ARUK-UCL.
DR   GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR   Gene3D; 4.10.40.20; -; 1.
DR   Gene3D; 6.20.200.20; -; 6.
DR   InterPro; IPR004094; Antistasin-like.
DR   InterPro; IPR045813; CRIM1_C.
DR   InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR011061; Hirudin/antistatin.
DR   InterPro; IPR000867; IGFBP-like.
DR   InterPro; IPR001007; VWF_dom.
DR   PANTHER; PTHR46439; CYSTEINE-RICH MOTOR NEURON 1 PROTEIN; 1.
DR   PANTHER; PTHR46439:SF1; CYSTEINE-RICH MOTOR NEURON 1 PROTEIN; 1.
DR   Pfam; PF02822; Antistasin; 4.
DR   Pfam; PF19442; CRIM1_C; 1.
DR   Pfam; PF00219; IGFBP; 1.
DR   Pfam; PF00093; VWC; 6.
DR   SMART; SM00121; IB; 1.
DR   SMART; SM00214; VWC; 6.
DR   SMART; SM00215; VWC_out; 4.
DR   SUPFAM; SSF57603; FnI-like domain; 6.
DR   SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR   SUPFAM; SSF57262; Leech antihemostatic proteins; 3.
DR   PROSITE; PS51252; ANTISTASIN; 4.
DR   PROSITE; PS51323; IGFBP_N_2; 1.
DR   PROSITE; PS01208; VWFC_1; 6.
DR   PROSITE; PS50184; VWFC_2; 6.
DR   Genevisible; Q9NZV1; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Membrane; Phosphoprotein; Reference proteome; Repeat; Secreted; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..34
FT                   /evidence="ECO:0000269|PubMed:12805376,
FT                   ECO:0000269|PubMed:15340161"
FT   CHAIN           35..1036
FT                   /note="Cysteine-rich motor neuron 1 protein"
FT                   /id="PRO_0000021001"
FT   CHAIN           ?..1036
FT                   /note="Processed cysteine-rich motor neuron 1 protein"
FT                   /id="PRO_0000296243"
FT   TOPO_DOM        35..939
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        940..960
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        961..1036
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          35..112
FT                   /note="IGFBP N-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DOMAIN          334..391
FT                   /note="VWFC 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          401..457
FT                   /note="VWFC 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          469..498
FT                   /note="Antistasin-like 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00582"
FT   DOMAIN          505..532
FT                   /note="Antistasin-like 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00582"
FT   DOMAIN          539..564
FT                   /note="Antistasin-like 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00582"
FT   DOMAIN          567..592
FT                   /note="Antistasin-like 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00582"
FT   DOMAIN          606..663
FT                   /note="VWFC 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          677..735
FT                   /note="VWFC 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          751..809
FT                   /note="VWFC 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          817..874
FT                   /note="VWFC 6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   MOTIF           314..316
FT                   /note="Cell attachment site"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         1035
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163"
FT   CARBOHYD        71
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        113
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        330
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        474
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        746
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        37..60
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        40..62
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        45..63
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        51..66
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        74..90
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        84..109
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   VARIANT         502
FT                   /note="E -> K (in dbSNP:rs12997487)"
FT                   /id="VAR_050907"
FT   VARIANT         781
FT                   /note="V -> I (in dbSNP:rs59929305)"
FT                   /id="VAR_061625"
FT   CONFLICT        433
FT                   /note="C -> F (in Ref. 2; BAD92376)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1036 AA;  113738 MW;  10CBF02A5C579C27 CRC64;
     MYLVAGDRGL AGCGHLLVSL LGLLLLLARS GTRALVCLPC DESKCEEPRN CPGSIVQGVC
     GCCYTCASQR NESCGGTFGI YGTCDRGLRC VIRPPLNGDS LTEYEAGVCE DENWTDDQLL
     GFKPCNENLI AGCNIINGKC ECNTIRTCSN PFEFPSQDMC LSALKRIEEE KPDCSKARCE
     VQFSPRCPED SVLIEGYAPP GECCPLPSRC VCNPAGCLRK VCQPGNLNIL VSKASGKPGE
     CCDLYECKPV FGVDCRTVEC PPVQQTACPP DSYETQVRLT ADGCCTLPTR CECLSGLCGF
     PVCEVGSTPR IVSRGDGTPG KCCDVFECVN DTKPACVFNN VEYYDGDMFR MDNCRFCRCQ
     GGVAICFTAQ CGEINCERYY VPEGECCPVC EDPVYPFNNP AGCYANGLIL AHGDRWREDD
     CTFCQCVNGE RHCVATVCGQ TCTNPVKVPG ECCPVCEEPT IITVDPPACG ELSNCTLTGK
     DCINGFKRDH NGCRTCQCIN TEELCSERKQ GCTLNCPFGF LTDAQNCEIC ECRPRPKKCR
     PIICDKYCPL GLLKNKHGCD ICRCKKCPEL SCSKICPLGF QQDSHGCLIC KCREASASAG
     PPILSGTCLT VDGHHHKNEE SWHDGCRECY CLNGREMCAL ITCPVPACGN PTIHPGQCCP
     SCADDFVVQK PELSTPSICH APGGEYFVEG ETWNIDSCTQ CTCHSGRVLC ETEVCPPLLC
     QNPSRTQDSC CPQCTDQPFR PSLSRNNSVP NYCKNDEGDI FLAAESWKPD VCTSCICIDS
     VISCFSESCP SVSCERPVLR KGQCCPYCIE DTIPKKVVCH FSGKAYADEE RWDLDSCTHC
     YCLQGQTLCS TVSCPPLPCV EPINVEGSCC PMCPEMYVPE PTNIPIEKTN HRGEVDLEVP
     LWPTPSENDI VHLPRDMGHL QVDYRDNRLH PSEDSSLDSI ASVVVPIIIC LSIIIAFLFI
     NQKKQWIPLL CWYRTPTKPS SLNNQLVSVD CKKGTRVQVD SSQRMLRIAE PDARFSGFYS
     MQKQNHLQAD NFYQTV
//