Q9H2X0 (CHRD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Chordin

Gene names

Name:	CHRD
ORF Names:	UNQ217/PRO243

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	955 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Dorsalizing factor. Key developmental protein that dorsalizes early vertebrate embryonic tissues by binding to ventralizing TGF-beta family bone morphogenetic proteins (BMPs) and sequestering them in latent complexes By similarity.
Subunit structure	Interacts with TWSG1 and/or BMP4 By similarity.
Subcellular location	Secreted By similarity.
Tissue specificity	Expressed at the highest level in liver.
Post-translational modification	Cleaved by tolloid proteases; cleavage participates in dorsoventral patterning during early development By similarity.
Sequence similarities	Belongs to the chordin family. Contains 4 CHRD domains. Contains 4 VWFC domains.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal
Molecular function	Developmental protein
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway involved in spinal cord dorsal/ventral patterning Inferred from mutant phenotype Ref.1. Source: BHF-UCL floor plate development Traceable author statement PubMed 11790302. Source: BHF-UCL forebrain development Inferred from electronic annotation. Source: Compara gastrulation with mouth forming second Inferred from electronic annotation. Source: Compara mesoderm formation Inferred from electronic annotation. Source: Compara negative regulation of BMP signaling pathway Inferred from mutant phenotype Ref.1. Source: BHF-UCL negative regulation of cell migration Inferred from direct assay PubMed 16449796. Source: BHF-UCL negative regulation of osteoblast differentiation Inferred from mutant phenotype PubMed 18533030. Source: BHF-UCL osteoblast differentiation Inferred from electronic annotation. Source: Compara positive regulation of cell adhesion Inferred from direct assay PubMed 16449796. Source: BHF-UCL positive regulation of mesenchymal cell proliferation Inferred from mutant phenotype PubMed 18533030. Source: BHF-UCL skeletal system development Traceable author statement Ref.4. Source: UniProtKB
Cellular_component	extracellular space Non-traceable author statement PubMed 16449796. Source: BHF-UCL
Molecular_function	cytokine binding Non-traceable author statement PubMed 16449796. Source: BHF-UCL heparin binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SMAD3	P84022	2	EBI-947551,EBI-347161

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q9H2X0-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9H2X0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     85-86: PQ → GP
     87-955: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 3 (identifier: Q9H2X0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     85-94: PQWGRRTRGP → TGTLRPREMK
     95-955: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 4 (identifier: Q9H2X0-4)

The sequence of this isoform differs from the canonical sequence as follows:
     328-350: GLTQVPLRLQILHQGQLLRELQA → DSTPGAATARTSGQCLSPGTRLC
     351-955: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 5 (identifier: Q9H2X0-5)

The sequence of this isoform differs from the canonical sequence as follows:
     441-480: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Chain	27 – 955	929	Chordin		PRO_0000005364
Regions
	Domain	49 – 126	78	VWFC 1
	Domain	168 – 277	110	CHRD 1
	Domain	279 – 402	124	CHRD 2
	Domain	403 – 524	122	CHRD 3
	Domain	530 – 650	121	CHRD 4
	Domain	703 – 763	61	VWFC 2
	Domain	784 – 850	67	VWFC 3
	Domain	872 – 932	61	VWFC 4
Amino acid modifications
	Glycosylation	217	1	N-linked (GlcNAc...) Potential
	Glycosylation	351	1	N-linked (GlcNAc...) Potential
	Glycosylation	365	1	N-linked (GlcNAc...) Potential
	Glycosylation	434	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	85 – 94	10	PQWGRRTRGP → TGTLRPREMK in isoform 3.		VSP_001071
	Alternative sequence	85 – 86	2	PQ → GP in isoform 2.		VSP_001069
	Alternative sequence	87 – 955	869	Missing in isoform 2.		VSP_001070
	Alternative sequence	95 – 955	861	Missing in isoform 3.		VSP_001072
	Alternative sequence	328 – 350	23	GLTQV…RELQA → DSTPGAATARTSGQCLSPGT RLC in isoform 4.		VSP_001073
	Alternative sequence	351 – 955	605	Missing in isoform 4.		VSP_001074
	Alternative sequence	441 – 480	40	Missing in isoform 5.		VSP_001075
	Natural variant	94	1	P → S. Corresponds to variant rs34095724 [ dbSNP | Ensembl ].		VAR_048727
	Natural variant	630	1	M → L. Ref.1 Ref.4 Corresponds to variant rs16858780 [ dbSNP | Ensembl ].		VAR_021517
Experimental info
	Sequence conflict	70	1	E → Q in AAQ89285. Ref.2
	Sequence conflict	115 – 118	4	RQLP → QVAA in AAC69835. Ref.4
	Sequence conflict	189	1	V → A in AAC69835. Ref.4
	Sequence conflict	216	1	S → P in AAC69835. Ref.4
	Sequence conflict	674	1	T → P in AAC69835. Ref.4
	Sequence conflict	939	1	Missing in AAQ89285. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 28, 2006. Version 2. Checksum: 53F9D9F39A517686	FASTA	955	102,032
	10 20 30 40 50 60 MPSLPAPPAP LLLLGLLLLG SRPARGAGPE PPVLPIRSEK EPLPVRGAAG CTFGGKVYAL 70 80 90 100 110 120 DETWHPDLGE PFGVMRCVLC ACEAPQWGRR TRGPGRVSCK NIKPECPTPA CGQPRQLPGH 130 140 150 160 170 180 CCQTCPQERS SSERQPSGLS FEYPRDPEHR SYSDRGEPGA EERARGDGHT DFVALLTGPR 190 200 210 220 230 240 SQAVARARVS LLRSSLRFSI SYRRLDRPTR IRFSDSNGSV LFEHPAAPTQ DGLVCGVWRA 250 260 270 280 290 300 VPRLSLRLLR AEQLHVALVT LTHPSGEVWG PLIRHRALAA ETFSAILTLE GPPQQGVGGI 310 320 330 340 350 360 TLLTLSDTED SLHFLLLFRG LLEPRSGGLT QVPLRLQILH QGQLLRELQA NVSAQEPGFA 370 380 390 400 410 420 EVLPNLTVQE MDWLVLGELQ MALEWAGRPG LRISGHIAAR KSCDVLQSVL CGADALIPVQ 430 440 450 460 470 480 TGAAGSASLT LLGNGSLIYQ VQVVGTSSEV VAMTLETKPQ RRDQRTVLCH MAGLQPGGHT 490 500 510 520 530 540 AVGICPGLGA RGAHMLLQNE LFLNVGTKDF PDGELRGHVA ALPYCGHSAR HDTLPVPLAG 550 560 570 580 590 600 ALVLPPVKSQ AAGHAWLSLD THCHLHYEVL LAGLGGSEQG TVTAHLLGPP GTPGPRRLLK 610 620 630 640 650 660 GFYGSEAQGV VKDLEPELLR HLAKGMASLM ITTKGSPRGE LRGQVHIANQ CEVGGLRLEA 670 680 690 700 710 720 AGAEGVRALG APDTASAAPP VVPGLPALAP AKPGGPGRPR DPNTCFFEGQ QRPHGARWAP 730 740 750 760 770 780 NYDPLCSLCT CQRRTVICDP VVCPPPSCPH PVQAPDQCCP VCPEKQDVRD LPGLPRSRDP 790 800 810 820 830 840 GEGCYFDGDR SWRAAGTRWH PVVPPFGLIK CAVCTCKGGT GEVHCEKVQC PRLACAQPVR 850 860 870 880 890 900 VNPTDCCKQC PVGSGAHPQL GDPMQADGPR GCRFAGQWFP ESQSWHPSVP PFGEMSCITC 910 920 930 940 950 RCGAGVPHCE RDDCSLPLSC GSGKESRCCS RCTAHRRPAP ETRTDPELEK EAEGS
	Isoform 2 [UniParc]. Checksum: 0679D7166DF9F994	FASTA	86	8,897
	10 20 30 40 50 60 MPSLPAPPAP LLLLGLLLLG SRPARGAGPE PPVLPIRSEK EPLPVRGAAG CTFGGKVYAL 70 80 DETWHPDLGE PFGVMRCVLC ACEAGP
	Isoform 3 [UniParc]. Checksum: 74479F0AE711A2C4	FASTA	94	9,913
	10 20 30 40 50 60 MPSLPAPPAP LLLLGLLLLG SRPARGAGPE PPVLPIRSEK EPLPVRGAAG CTFGGKVYAL 70 80 90 DETWHPDLGE PFGVMRCVLC ACEATGTLRP REMK
	Isoform 4 [UniParc]. Checksum: F18D4B0ED3EB6A98	FASTA	350	37,782
	10 20 30 40 50 60 MPSLPAPPAP LLLLGLLLLG SRPARGAGPE PPVLPIRSEK EPLPVRGAAG CTFGGKVYAL 70 80 90 100 110 120 DETWHPDLGE PFGVMRCVLC ACEAPQWGRR TRGPGRVSCK NIKPECPTPA CGQPRQLPGH 130 140 150 160 170 180 CCQTCPQERS SSERQPSGLS FEYPRDPEHR SYSDRGEPGA EERARGDGHT DFVALLTGPR 190 200 210 220 230 240 SQAVARARVS LLRSSLRFSI SYRRLDRPTR IRFSDSNGSV LFEHPAAPTQ DGLVCGVWRA 250 260 270 280 290 300 VPRLSLRLLR AEQLHVALVT LTHPSGEVWG PLIRHRALAA ETFSAILTLE GPPQQGVGGI 310 320 330 340 350 TLLTLSDTED SLHFLLLFRG LLEPRSGDST PGAATARTSG QCLSPGTRLC
	Isoform 5 [UniParc]. Checksum: 506ADC62F09ED062	FASTA	915	97,731
	10 20 30 40 50 60 MPSLPAPPAP LLLLGLLLLG SRPARGAGPE PPVLPIRSEK EPLPVRGAAG CTFGGKVYAL 70 80 90 100 110 120 DETWHPDLGE PFGVMRCVLC ACEAPQWGRR TRGPGRVSCK NIKPECPTPA CGQPRQLPGH 130 140 150 160 170 180 CCQTCPQERS SSERQPSGLS FEYPRDPEHR SYSDRGEPGA EERARGDGHT DFVALLTGPR 190 200 210 220 230 240 SQAVARARVS LLRSSLRFSI SYRRLDRPTR IRFSDSNGSV LFEHPAAPTQ DGLVCGVWRA 250 260 270 280 290 300 VPRLSLRLLR AEQLHVALVT LTHPSGEVWG PLIRHRALAA ETFSAILTLE GPPQQGVGGI 310 320 330 340 350 360 TLLTLSDTED SLHFLLLFRG LLEPRSGGLT QVPLRLQILH QGQLLRELQA NVSAQEPGFA 370 380 390 400 410 420 EVLPNLTVQE MDWLVLGELQ MALEWAGRPG LRISGHIAAR KSCDVLQSVL CGADALIPVQ 430 440 450 460 470 480 TGAAGSASLT LLGNGSLIYQ AVGICPGLGA RGAHMLLQNE LFLNVGTKDF PDGELRGHVA 490 500 510 520 530 540 ALPYCGHSAR HDTLPVPLAG ALVLPPVKSQ AAGHAWLSLD THCHLHYEVL LAGLGGSEQG 550 560 570 580 590 600 TVTAHLLGPP GTPGPRRLLK GFYGSEAQGV VKDLEPELLR HLAKGMASLM ITTKGSPRGE 610 620 630 640 650 660 LRGQVHIANQ CEVGGLRLEA AGAEGVRALG APDTASAAPP VVPGLPALAP AKPGGPGRPR 670 680 690 700 710 720 DPNTCFFEGQ QRPHGARWAP NYDPLCSLCT CQRRTVICDP VVCPPPSCPH PVQAPDQCCP 730 740 750 760 770 780 VCPEKQDVRD LPGLPRSRDP GEGCYFDGDR SWRAAGTRWH PVVPPFGLIK CAVCTCKGGT 790 800 810 820 830 840 GEVHCEKVQC PRLACAQPVR VNPTDCCKQC PVGSGAHPQL GDPMQADGPR GCRFAGQWFP 850 860 870 880 890 900 ESQSWHPSVP PFGEMSCITC RCGAGVPHCE RDDCSLPLSC GSGKESRCCS RCTAHRRPAP 910 ETRTDPELEK EAEGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human chordin gene encodes several differentially expressed spliced variants with distinct BMP opposing activities." Millet C., Lemaire P., Orsetti B., Guglielmi P., Francois V. Mech. Dev. 106:85-96(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), VARIANT LEU-630.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"Coding sequence and expression patterns of mouse chordin and mapping of the cognate mouse chrd and human CHRD genes." Pappano W.N., Scott I.C., Clark T.G., Eddy R.L., Shows T.B., Greenspan D.S. Genomics 52:236-239(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 115-955 (ISOFORM 5), VARIANT LEU-630.
[5]	"BMP-binding modules in chordin: a model for signalling regulation in the extracellular space." Larrain J., Bachiller D., Lu B., Agius E., Piccolo S., De Robertis E.M. Development 127:821-830(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 51-125; 705-762; 784-850 AND 872-932.
[6]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF209928 mRNA. Translation: AAG35767.1. AF209929 mRNA. Translation: AAG35768.1. AF209930 mRNA. Translation: AAG35769.1. AF283325 mRNA. Translation: AAG35784.1. AY358926 mRNA. Translation: AAQ89285.1. BC112345 mRNA. Translation: AAI12346.1. AF076612 mRNA. Translation: AAC69835.1. AF136632 Genomic DNA. Translation: AAF70236.1. AF136633 Genomic DNA. Translation: AAF70237.1. AF136634 Genomic DNA. Translation: AAF70238.1. AF136635 Genomic DNA. Translation: AAF70239.1.
IPI	IPI00221160. IPI00221161. IPI00221162. IPI00306710. IPI00719497.
RefSeq	NP_003732.2. NM_003741.2.
UniGene	Hs.166186.
3D structure databases
ProteinModelPortal	Q9H2X0.
SMR	Q9H2X0. Positions 46-131, 700-766, 781-855, 868-938.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48857N.
IntAct	Q9H2X0. 10 interactions.
MINT	MINT-2817631.
PTM databases
PhosphoSite	Q9H2X0.
Polymorphism databases
DMDM	118572631.
Proteomic databases
PaxDb	Q9H2X0.
PRIDE	Q9H2X0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000204604; ENSP00000204604; ENSG00000090539. ENST00000310236; ENSP00000308559; ENSG00000090539. ENST00000348986; ENSP00000334036; ENSG00000090539. ENST00000356534; ENSP00000348930; ENSG00000090539. ENST00000420973; ENSP00000392794; ENSG00000090539. ENST00000448472; ENSP00000408624; ENSG00000090539.
GeneID	8646.
KEGG	hsa:8646.
UCSC	uc003fov.3. human. uc010hyc.3. human.
Organism-specific databases
CTD	8646.
GeneCards	GC03P184097.
H-InvDB	HIX0003911.
HGNC	HGNC:1949. CHRD.
HPA	CAB020705. HPA035827.
MIM	603475. gene.
neXtProt	NX_Q9H2X0.
PharmGKB	PA26482.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG85639.
HOVERGEN	HBG005330.
InParanoid	Q9H2X0.
KO	K04657.
OMA	GARWAPN.
OrthoDB	EOG4T1HKS.
Enzyme and pathway databases
Pathway_Interaction_DB	bmppathway. BMP receptor signaling.
Gene expression databases
ArrayExpress	Q9H2X0.
Bgee	Q9H2X0.
Genevestigator	Q9H2X0.
GermOnline	ENSG00000090539. Homo sapiens.
Family and domain databases
InterPro	IPR016353. Chordin. IPR010895. CHRD. IPR001007. VWF_C. [Graphical view]
Pfam	PF07452. CHRD. 4 hits. PF00093. VWC. 3 hits. [Graphical view]
PIRSF	PIRSF002496. Chordin. 1 hit.
SMART	SM00754. CHRD. 4 hits. SM00214. VWC. 4 hits. [Graphical view]
PROSITE	PS50933. CHRD. 4 hits. PS01208. VWFC_1. 2 hits. PS50184. VWFC_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8646.
NextBio	32415.
PMAP-CutDB	Q9H2X0.
SOURCE	Search...

Entry information

Entry name

CHRD_HUMAN

Accession

Primary (citable) accession number: Q9H2X0
Secondary accession number(s): O95254 , Q2M1I8, Q6UW83, Q9H2D3, Q9H2W8, Q9H2W9, Q9P0Z2, Q9P0Z3, Q9P0Z4, Q9P0Z5

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	November 28, 2006
Last modified:	May 1, 2013
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.