ID   KCP_MOUSE               Reviewed;        1550 AA.
AC   Q3U492; E9QJU0; Q56NI8;
DT   05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   27-MAR-2024, entry version 111.
DE   RecName: Full=Kielin/chordin-like protein;
DE   AltName: Full=Cysteine-rich BMP regulator 2;
DE   AltName: Full=Cysteine-rich motor neuron 2 protein;
DE            Short=CRIM-2;
DE   AltName: Full=Kielin/chordin-like protein 1;
DE            Short=KCP-1;
DE   Flags: Precursor;
GN   Name=Kcp; Synonyms=Crim2, Kcp1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH BMP7,
RP   TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, AND
RP   INDUCTION BY RENAL STRESSES.
RC   STRAIN=FVB/N;
RX   PubMed=15793581; DOI=10.1038/nm1217;
RA   Lin J., Patel S.R., Cheng X., Cho E.A., Levitan I., Ullenbruch M.,
RA   Phan S.H., Park J.M., Dressler G.R.;
RT   "Kielin/chordin-like protein, a novel enhancer of BMP signaling, attenuates
RT   renal fibrotic disease.";
RL   Nat. Med. 11:387-393(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=NOD;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   INTERACTION WITH ACTIVIN A AND TGFB1.
RX   PubMed=16738323; DOI=10.1128/mcb.02127-05;
RA   Lin J., Patel S.R., Wang M., Dressler G.R.;
RT   "The cysteine-rich domain protein KCP is a suppressor of transforming
RT   growth factor beta/activin signaling in renal epithelia.";
RL   Mol. Cell. Biol. 26:4577-4585(2006).
CC   -!- FUNCTION: Enhances bone morphogenetic protein (BMP) signaling in a
CC       paracrine manner. In contrast, it inhibits both the activin-A and
CC       TGFB1-mediated signaling pathways. {ECO:0000269|PubMed:15793581}.
CC   -!- SUBUNIT: Interacts with BMP7 and, by doing so, enhances binding to the
CC       type I receptors that contains cytoplasmic serine-/threonine protein
CC       kinase domains. Also able to interact with activin-A and TGFB1.
CC       {ECO:0000269|PubMed:15793581, ECO:0000269|PubMed:16738323}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15793581}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q3U492-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q3U492-2; Sequence=VSP_031232, VSP_031233;
CC   -!- TISSUE SPECIFICITY: Weakly expressed in embryonic kidney and brain. Not
CC       expressed in adult tissues and several cell lines.
CC       {ECO:0000269|PubMed:15793581}.
CC   -!- DEVELOPMENTAL STAGE: Prominently expressed in two areas, the limb buds
CC       and the developing kidney, with diffuse staining in the central nervous
CC       system. At 9.5 dpc the limb bud mesenchyme is positive. Expression in
CC       the kidney region could be detected as early as 9 dpc in the
CC       intermediate mesoderm. By 10 dpc, the mesonephric tubules and nephric
CC       ducts are clearly positive. At later stages, high levels are localized
CC       to the developing tubules. At 18.5 dpc, it is localized to more mature
CC       renal tubules located in the developing cortex with little expression
CC       detected in the nephrogenic zone. {ECO:0000269|PubMed:15793581}.
CC   -!- INDUCTION: By renal stresses. {ECO:0000269|PubMed:15793581}.
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DR   EMBL; AY884211; AAX77677.1; -; mRNA.
DR   EMBL; AK154369; BAE32541.1; -; mRNA.
DR   EMBL; AC079276; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS57415.1; -. [Q3U492-1]
DR   RefSeq; NP_001025156.3; NM_001029985.4. [Q3U492-1]
DR   AlphaFoldDB; Q3U492; -.
DR   SMR; Q3U492; -.
DR   BioGRID; 237147; 1.
DR   STRING; 10090.ENSMUSP00000099135; -.
DR   GlyCosmos; Q3U492; 1 site, No reported glycans.
DR   GlyGen; Q3U492; 1 site.
DR   iPTMnet; Q3U492; -.
DR   PhosphoSitePlus; Q3U492; -.
DR   MaxQB; Q3U492; -.
DR   PaxDb; 10090-ENSMUSP00000099135; -.
DR   ProteomicsDB; 263507; -. [Q3U492-1]
DR   ProteomicsDB; 263508; -. [Q3U492-2]
DR   Antibodypedia; 73205; 30 antibodies from 13 providers.
DR   DNASU; 333088; -.
DR   Ensembl; ENSMUST00000078112.13; ENSMUSP00000077251.7; ENSMUSG00000059022.16. [Q3U492-2]
DR   Ensembl; ENSMUST00000101614.10; ENSMUSP00000099135.4; ENSMUSG00000059022.16. [Q3U492-1]
DR   GeneID; 333088; -.
DR   KEGG; mmu:333088; -.
DR   UCSC; uc009bdt.2; mouse. [Q3U492-1]
DR   AGR; MGI:2141640; -.
DR   CTD; 375616; -.
DR   MGI; MGI:2141640; Kcp.
DR   VEuPathDB; HostDB:ENSMUSG00000059022; -.
DR   eggNOG; KOG1216; Eukaryota.
DR   GeneTree; ENSGT00940000160243; -.
DR   HOGENOM; CLU_000367_0_0_1; -.
DR   InParanoid; Q3U492; -.
DR   OMA; CQECVVE; -.
DR   OrthoDB; 2906064at2759; -.
DR   PhylomeDB; Q3U492; -.
DR   TreeFam; TF106451; -.
DR   BioGRID-ORCS; 333088; 0 hits in 79 CRISPR screens.
DR   ChiTaRS; Kcp; mouse.
DR   PRO; PR:Q3U492; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; Q3U492; Protein.
DR   Bgee; ENSMUSG00000059022; Expressed in internal carotid artery and 152 other cell types or tissues.
DR   ExpressionAtlas; Q3U492; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IGI:MGI.
DR   GO; GO:0030513; P:positive regulation of BMP signaling pathway; IDA:MGI.
DR   CDD; cd19941; TIL; 1.
DR   Gene3D; 6.20.200.20; -; 11.
DR   Gene3D; 2.10.70.10; Complement Module, domain 1; 6.
DR   InterPro; IPR036084; Ser_inhib-like_sf.
DR   InterPro; IPR014853; VWF/SSPO/ZAN-like_Cys-rich_dom.
DR   InterPro; IPR001007; VWF_dom.
DR   InterPro; IPR001846; VWF_type-D.
DR   PANTHER; PTHR46698:SF5; -; 1.
DR   PANTHER; PTHR46698; CROSSVEINLESS 2; 1.
DR   Pfam; PF00093; VWC; 9.
DR   Pfam; PF00094; VWD; 1.
DR   SMART; SM00832; C8; 1.
DR   SMART; SM00214; VWC; 17.
DR   SMART; SM00215; VWC_out; 10.
DR   SMART; SM00216; VWD; 1.
DR   SUPFAM; SSF57603; FnI-like domain; 18.
DR   SUPFAM; SSF57567; Serine protease inhibitors; 1.
DR   PROSITE; PS01208; VWFC_1; 13.
DR   PROSITE; PS50184; VWFC_2; 14.
DR   PROSITE; PS51233; VWFD; 1.
DR   Genevisible; Q3U492; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Coiled coil; Disulfide bond; Glycoprotein;
KW   Reference proteome; Repeat; Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..1550
FT                   /note="Kielin/chordin-like protein"
FT                   /id="PRO_0000318587"
FT   DOMAIN          134..191
FT                   /note="VWFC 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          192..251
FT                   /note="VWFC 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          253..312
FT                   /note="VWFC 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          313..370
FT                   /note="VWFC 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          371..425
FT                   /note="VWFC 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          426..485
FT                   /note="VWFC 6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          486..544
FT                   /note="VWFC 7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          545..602
FT                   /note="VWFC 8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          603..661
FT                   /note="VWFC 9"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          665..724
FT                   /note="VWFC 10"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          725..781
FT                   /note="VWFC 11"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          782..840
FT                   /note="VWFC 12"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          841..902
FT                   /note="VWFC 13"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          903..958
FT                   /note="VWFC 14"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          959..1016
FT                   /note="VWFC 15"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          1017..1084
FT                   /note="VWFC 16"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          1085..1144
FT                   /note="VWFC 17"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          1148..1208
FT                   /note="VWFC 18"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          1212..1388
FT                   /note="VWFD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT   DOMAIN          1489..1542
FT                   /note="TIL"
FT   REGION          31..53
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          60..92
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        34..53
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        340
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        1214..1346
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT   DISULFID        1236..1387
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT   VAR_SEQ         1250..1255
FT                   /note="SVHVTN -> RWTSTQ (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15793581"
FT                   /id="VSP_031232"
FT   VAR_SEQ         1256..1550
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15793581"
FT                   /id="VSP_031233"
FT   CONFLICT        385
FT                   /note="F -> L (in Ref. 1; AAX77677)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        829
FT                   /note="L -> F (in Ref. 2; BAE32541)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1045
FT                   /note="Missing (in Ref. 1; AAX77677)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1147
FT                   /note="T -> N (in Ref. 2; BAE32541)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1550 AA;  166628 MW;  6E6630EDA239D744 CRC64;
     MAGARAALLP LLLHLGSLAL AARGGEVSRE QPRLADAISQ QQAPSHSLVP GETHQQQWCP
     LEERLERLEA EVTDLRKQNR ELQARVVQLE SCECWGPGHT CPEGARWEPD ACTACVCRDG
     TAHCGPQPNL PHCRGCSHNG QSYGHGETFS PDACTTCRCL AGTVQCQGPS CSELNCLESF
     IPPGECCPIC RPGCEYEGQL HQEGSSFLSS SNPCLQCSCL RSLVRCVPVK CQPSPCLNPV
     PRLGHCCPVC QASGCTEGNS HRDHGQEWTT PGDPCRICQC LEGHIQCRQR ECASLCPYPA
     RPLPGTCCPV CDGCFLNGRE HSSGEPVGSQ DPCSSCRCTN GSVQCEPLPC PPAPCRYPGR
     IPGQCCPVCD GCKYQGHEYR SQETFTLQEN GRCLRCVCQA GEVSCEEQDC PVTPCVRSAS
     GPQLCSACVL NGEEFAEGIQ WEPDDQPCTS CSCQDGVPVC RAVLCSPVPC QHPTQPPGAC
     CPSCDSCTYH SLVYANGQNF TDVDSPCQTC YCEDGTVRCS LINCPFTTCA KPQNGPGQCC
     PKCPDCILEA QVFVDGERFP HPRDPCQECW CQEGQAHCQL RACPSAPCVH PLPGTCCKND
     CTGCAFGGKE YPNGADFPHP TDPCRLCRCL SGNVQCLARR CPPLSCPQPV LTPGDCCPQC
     PDAPADCPQS GNMVPVRHQE HFFQPGDPCS RCLCLDGSVS CQRLTCPPAP CAHPRRDACC
     PSCDGCLYQG KEFASGERFP SPNVACHVCL CWEGSVKCEP RTCAPAQCPF PTREDCCPAC
     DSCDYLGVSY LSSQEFPDPR EACNLCTCLG GFVTCTRRPC EPPACSHPLI VPEHCCPTCQ
     GCLYHGITAA LGETLPDPLD PTCSLCTCEE GSMRCQKKPC PPAPCAHPSP GPCFCPVCRS
     CLSQGREHQD GEEFEGPEGS CERCRCLAGQ VSCTRLQCPS LPCLHQVTEP GTCCPRCTGC
     LARGEEHPEG SSWVPADSPC SSCMCHKGII TCAQVQCVSA CIWPQEGPSD CCPQCSGCEH
     GGRKYEPGES FQPGADPCEV CICKQKREGP PSLHCSRRQC PSLVGCPPSQ LLPPGPQHCC
     PTCAQALSNC TEDLVGSELV PPDPCYTCQC QDLTWLCTHR ACPELSCPLW ERHTTPGSCC
     PVCKDPTQSC MHQGRWVASG EQWAVDACTS CSCVAGTVHC QTQRCRKLAC SRDEVPALSP
     GSCCLRCLPR PASCMAFGDP HYRTFDGRLL HFQGSCSYVL AKDCHGEDFS VHVTNDDRGR
     RGVAWTQEVA VLLGTVAVRL LQGRTVMVDQ HTVTLPFLRE PLLYIELRGH TVILHAQPGL
     QVLWDGQSQV EVRVPSSYRG QTCGLCGNFN GFAQDDLQGP DGRLLPTEAS FGNSWKVPKG
     LGPGRPCSAG REVDPCRAAG YRARREANAR CGILKTSPFS HCHAVVPPEP FFAACVYDLC
     ACGPGSSSDT CLCDALEAYA SHCRQAGVTP VWRGPTLCVV GCPVDRGFVF DECGPPCPRT
     CFNRHIPLGE LAAHCVRPCV PGCQCPAGLV EHEGHCISPE VCPPVLLTGD
//