KCP_HUMAN
ID KCP_HUMAN Reviewed; 1568 AA.
AC Q6ZWJ8; A0A087WT73; Q8NBE0;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 3.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Kielin/chordin-like protein {ECO:0000305};
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 {ECO:0000312|HGNC:HGNC:17585}; Synonyms=CRIM2, KCP1;
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 [LARGE SCALE MRNA] (ISOFORMS 2 AND 4), AND VARIANTS
RP GLU-459 AND VAL-688.
RC TISSUE=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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). {ECO:0000250}.
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 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=Q6ZWJ8-3; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZWJ8-2; Sequence=VSP_059352, VSP_059356, VSP_059357;
CC Name=4;
CC IsoId=Q6ZWJ8-4; Sequence=VSP_059353, VSP_059354, VSP_059355;
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK122706; BAC85504.1; -; mRNA.
DR EMBL; AK090684; BAC03505.1; -; mRNA.
DR EMBL; AC025594; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF495713; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF510975; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471070; EAW83694.1; -; Genomic_DNA.
DR RefSeq; NP_001129386.1; NM_001135914.1.
DR RefSeq; NP_955381.2; NM_199349.2. [Q6ZWJ8-4]
DR AlphaFoldDB; Q6ZWJ8; -.
DR SMR; Q6ZWJ8; -.
DR STRING; 9606.ENSP00000479679; -.
DR GlyGen; Q6ZWJ8; 5 sites, 2 O-linked glycans (2 sites).
DR PhosphoSitePlus; Q6ZWJ8; -.
DR BioMuta; KCP; -.
DR DMDM; 218511989; -.
DR EPD; Q6ZWJ8; -.
DR jPOST; Q6ZWJ8; -.
DR MassIVE; Q6ZWJ8; -.
DR PeptideAtlas; Q6ZWJ8; -.
DR PRIDE; Q6ZWJ8; -.
DR ProteomicsDB; 68490; -. [Q6ZWJ8-2]
DR Antibodypedia; 73205; 25 antibodies from 13 providers.
DR DNASU; 375616; -.
DR Ensembl; ENST00000613019.4; ENSP00000477644.1; ENSG00000135253.16. [Q6ZWJ8-3]
DR GeneID; 375616; -.
DR KEGG; hsa:375616; -.
DR CTD; 375616; -.
DR DisGeNET; 375616; -.
DR GeneCards; KCP; -.
DR HGNC; HGNC:17585; KCP.
DR HPA; ENSG00000135253; Tissue enriched (kidney).
DR MIM; 609344; gene.
DR neXtProt; NX_Q6ZWJ8; -.
DR OpenTargets; ENSG00000135253; -.
DR PharmGKB; PA164721151; -.
DR VEuPathDB; HostDB:ENSG00000135253; -.
DR GeneTree; ENSGT00940000160243; -.
DR InParanoid; Q6ZWJ8; -.
DR OrthoDB; 1104860at2759; -.
DR PhylomeDB; Q6ZWJ8; -.
DR PathwayCommons; Q6ZWJ8; -.
DR BioGRID-ORCS; 375616; 6 hits in 201 CRISPR screens.
DR GenomeRNAi; 375616; -.
DR Pharos; Q6ZWJ8; Tdark.
DR PRO; PR:Q6ZWJ8; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q6ZWJ8; protein.
DR Bgee; ENSG00000135253; Expressed in metanephros cortex and 104 other tissues.
DR ExpressionAtlas; Q6ZWJ8; baseline and differential.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0036122; F:BMP binding; IBA:GO_Central.
DR GO; GO:0070700; F:BMP receptor binding; IBA:GO_Central.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IBA:GO_Central.
DR InterPro; IPR036084; Ser_inhib-like_sf.
DR InterPro; IPR014853; Unchr_dom_Cys-rich.
DR InterPro; IPR001007; VWF_dom.
DR InterPro; IPR001846; VWF_type-D.
DR Pfam; PF00093; VWC; 9.
DR Pfam; PF00094; VWD; 1.
DR SMART; SM00832; C8; 1.
DR SMART; SM00214; VWC; 19.
DR SMART; SM00215; VWC_out; 8.
DR SMART; SM00216; VWD; 1.
DR SUPFAM; SSF57567; SSF57567; 1.
DR PROSITE; PS01208; VWFC_1; 13.
DR PROSITE; PS50184; VWFC_2; 16.
DR PROSITE; PS51233; VWFD; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Coiled coil; Disulfide bond; Glycoprotein;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1568
FT /note="Kielin/chordin-like protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000318586"
FT DOMAIN 136..193
FT /note="VWFC 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 194..253
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 312..370
FT /note="VWFC 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 426..485
FT /note="VWFC 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 485..544
FT /note="VWFC 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 544..602
FT /note="VWFC 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 602..661
FT /note="VWFC 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 667..725
FT /note="VWFC 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 725..782
FT /note="VWFC 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 782..841
FT /note="VWFC 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 900..959
FT /note="VWFC 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 959..1017
FT /note="VWFC 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 1017..1085
FT /note="VWFC 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 1082..1145
FT /note="VWFC 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 1149..1209
FT /note="VWFC 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 1213..1389
FT /note="VWFD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT DOMAIN 1483..1543
FT /note="TIL"
FT REGION 27..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 60..87
FT /evidence="ECO:0000255"
FT COMPBIAS 35..49
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 CARBOHYD 499
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1090
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 1215..1347
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT DISULFID 1237..1388
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT VAR_SEQ 1..1174
FT /note="Missing (in isoform 2)"
FT /id="VSP_059352"
FT VAR_SEQ 163..193
FT /note="TGAVQCQGPSCSELNCLESCTPPGECCPICR -> EGTITCNQKPCPRGPCP
FT EPGACCPHCK (in isoform 4)"
FT /id="VSP_059353"
FT VAR_SEQ 784..818
FT /note="CEYLGESYLSNQEFPDPREPCNLCTCLGGFVTCGR -> EGHGIGSCRGGMR
FT ETRGLGQNNLYCPRVDLKYLLQ (in isoform 4)"
FT /id="VSP_059354"
FT VAR_SEQ 819..1568
FT /note="Missing (in isoform 4)"
FT /id="VSP_059355"
FT VAR_SEQ 1379..1468
FT /note="SEGLWPGRPCSAGREVDPCRAAGYRARREANARCGVLKSSPFSRCHAVVPPE
FT PFFAACVYDLCACGPGSSADACLCDALEAYASHCRQAG -> QEGRGYPPGLELPPVLL
FT QMEWSRRAQEQLLWDLELLTGVELGLFWPPQAQFFGPRGQAQQAWSQCCQPGGSTGGDP
FT EQPILKASCDGSRL (in isoform 2)"
FT /id="VSP_059356"
FT VAR_SEQ 1469..1568
FT /note="Missing (in isoform 2)"
FT /id="VSP_059357"
FT VARIANT 47
FT /note="G -> E (in dbSNP:rs7787221)"
FT /id="VAR_038783"
FT VARIANT 459
FT /note="K -> E (in dbSNP:rs7782976)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_059625"
FT VARIANT 688
FT /note="D -> V (in dbSNP:rs3734971)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_059626"
FT VARIANT 1193
FT /note="P -> R (in dbSNP:rs7786641)"
FT /id="VAR_059627"
FT CONFLICT 214
FT /note="N -> K (in Ref. 1; BAC85504)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1568 AA; 166935 MW; 7C63B5766B3EA7F3 CRC64;
MAGVGAAALS LLLHLGALAL AAGAEGGAVP REPPGQQTTA HSSVLAGNSQ EQWHPLREWL
GRLEAAVMEL REQNKDLQTR VRQLESCECH PASPQCWGLG RAWPEGARWE PDACTACVCQ
DGAAHCGPQA HLPHCRGCSQ NGQTYGNGET FSPDACTTCR CLTGAVQCQG PSCSELNCLE
SCTPPGECCP ICRPGCDYEG QLYEEGVTFL SSSNPCLQCT CLRSRVRCMA LKCPPSPCPE
PVLRPGHCCP TCQGCTEGGS HWEHGQEWTT PGDPCRICRC LEGHIQCRQR ECASLCPYPA
RPLPGTCCPV CDGCFLNGRE HRSGEPVGSG DPCSHCRCAN GSVQCEPLPC PPVPCRHPGK
IPGQCCPVCD GCEYQGHQYQ SQETFRLQER GLCVRCSCQA GEVSCEEQEC PVTPCALPAS
GRQLCPACEL DGEEFAEGVQ WEPDGRPCTA CVCQDGVPKC GAVLCPPAPC QHPTQPPGAC
CPSCDSCTYH SQVYANGQNF TDADSPCHAC HCQDGTVTCS LVDCPPTTCA RPQSGPGQCC
PRCPDCILEE EVFVDGESFS HPRDPCQECR CQEGHAHCQP RPCPRAPCAH PLPGTCCPND
CSGCAFGGKE YPSGADFPHP SDPCRLCRCL SGNVQCLARR CVPLPCPEPV LLPGECCPQC
PAAPAPAGCP RPGAAHARHQ EYFSPPGDPC RRCLCLDGSV SCQRLPCPPA PCAHPRQGPC
CPSCDGCLYQ GKEFASGERF PSPTAACHLC LCWEGSVSCE PKACAPALCP FPARGDCCPD
CDGCEYLGES YLSNQEFPDP REPCNLCTCL GGFVTCGRRP CEPPGCSHPL IPSGHCCPTC
QGCRYHGVTT ASGETLPDPL DPTCSLCTCQ EGSMRCQKKP CPPALCPHPS PGPCFCPVCH
SCLSQGREHQ DGEEFEGPAG SCEWCRCQAG QVSCVRLQCP PLPCKLQVTE RGSCCPRCRG
CLAHGEEHPE GSRWVPPDSA CSSCVCHEGV VTCARIQCIS SCAQPRQGPH DCCPQCSDCE
HEGRKYEPGE SFQPGADPCE VCICEPQPEG PPSLRCHRRQ CPSLVGCPPS QLLPPGPQHC
CPTCAEALSN CSEGLLGSEL APPDPCYTCQ CQDLTWLCIH QACPELSCPL SERHTPPGSC
CPVCRAPTQS CVHQGREVAS GERWTVDTCT SCSCMAGTVR CQSQRCSPLS CGPDKAPALS
PGSCCPRCLP RPASCMAFGD PHYRTFDGRL LHFQGSCSYV LAKDCHSGDF SVHVTNDDRG
RSGVAWTQEV AVLLGDMAVR LLQDGAVTVD GHPVALPFLQ EPLLYVELRG HTVILHAQPG
LQVLWDGQSQ VEVSVPGSYQ GRTCGLCGNF NGFAQDDLQG PEGLLLPSEA AFGNSWQVSE
GLWPGRPCSA GREVDPCRAA GYRARREANA RCGVLKSSPF SRCHAVVPPE PFFAACVYDL
CACGPGSSAD ACLCDALEAY ASHCRQAGVT PTWRGPTLCV VGCPLERGFV FDECGPPCPR
TCFNQHIPLG ELAAHCVRPC VPGCQCPAGL VEHEAHCIPP EACPQVLLTG DQPLGARPSP
SREPQETP
