Reviewed, UniProtKB/Swiss-Prot P36896 (ACV1B_HUMAN)

Names and origin

Protein names

Recommended name:
    Activin receptor type-1B
    EC=2.7.11.30
Alternative name(s):
    ACTR-IB
    Serine/threonine-protein kinase receptor R2
      Short name=SKR2
    Activin receptor-like kinase 4
      Short name=ALK-4

Gene names

Name:	ACVR1B
Synonyms:	ACVRLK4, ALK4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	505 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	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Phosphorylates TTRAP. Ref.7
Catalytic activity	ATP + [receptor-protein] = ADP + [receptor-protein] phosphate.
Cofactor	Magnesium or manganese By similarity.
Subunit structure	Interacts with AIP1. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3. Interacts with TTRAP By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed in many tissues, most strongly in kidney, pancreas, brain, lung, and liver.
Post-translational modification	Autophosphorylated. Ref.7 Ref.6
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. Contains 1 GS domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Serine/threonine-protein kinase Transferase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	G1/S transition of mitotic cell cycle Inferred from direct assay. Source: HGNC induction of apoptosis Inferred from mutant phenotype. Source: HGNC negative regulation of cell growth Inferred from direct assay. Source: HGNC peptidyl-threonine phosphorylation Ref.7 Inferred from direct assay. Source: UniProtKB positive regulation of activin receptor signaling pathway Inferred from direct assay. Source: UniProtKB positive regulation of erythrocyte differentiation Inferred from direct assay. Source: HGNC protein amino acid autophosphorylation Ref.7 Inferred from direct assay. Source: UniProtKB regulation of transcription Inferred from direct assay. Source: HGNC transmembrane receptor protein serine/threonine kinase signaling pathway Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cell surface Inferred from direct assay. Source: HGNC integral to plasma membrane Inferred from direct assay. Source: HGNC
Molecular function	ATP binding Inferred from direct assay. Source: HGNC SMAD binding Inferred from direct assay. Source: HGNC activin receptor activity, type I Traceable author statement. Source: HGNC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin protein ligase binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P36896-1) Also known as: SKR2-1; 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: P36896-2) Also known as: SKR2-2; The sequence of this isoform differs from the canonical sequence as follows:      465-505: ALRVMGKMMRECWYANGAARLTALRIKKTLSQLSVQEDVKI → VRSWPPAAFPSA
Isoform 3 (identifier: P36896-3) Also known as: SKR2-3; The sequence of this isoform differs from the canonical sequence as follows:      422-505: VHEEYQLPYY...QLSVQEDVKI → TFLFCLCSYL...RLFFRDQFVE
Sequence annotation (Features)
	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
	Natural variant	478	1	R → H

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 505	482	Activin receptor type-1B		PRO_0000024417
Regions
	Topological domain	24 – 126	103	Extracellular Potential
	Transmembrane	127 – 149	23	Potential
	Topological domain	150 – 505	356	Cytoplasmic Potential
	Domain	177 – 206	30	GS
	Domain	207 – 497	291	Protein kinase
	Nucleotide binding	213 – 221	9	ATP By similarity
Sites
	Active site	335	1	Proton acceptor By similarity
	Binding site	234	1	ATP By similarity
Amino acid modifications
	Modified residue	380	1	Phosphotyrosine Ref.6
	Glycosylation	43	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	422 – 505	84	VHEEY…EDVKI → TFLFCLCSYLPFQDAGSPKA VLLPPFFLQPVGCLLPEPES SFKVAIKGVEVAVLRVRLFF RDQFVE in isoform 3.		VSP_004953
	Alternative sequence	465 – 505	41	ALRVM…EDVKI → VRSWPPAAFPSA in isoform 2.		VSP_004954
	Natural variant	146	1	F → L		VAR_041406
	Natural variant	408	1	L → V: dbSNP rs928906.		VAR_011716
Experimental info
	Sequence conflict	56	1	I → F in AAA60555. Ref.3
	Sequence conflict	56	1	I → F in AAA60556. Ref.3
	Sequence conflict	222 – 223	2	WR → MA in AAA60555. Ref.3
	Sequence conflict	222 – 223	2	WR → MA in AAA60556. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (SKR2-1) [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 40A6C65CAA4C7573	FASTA	505	56,807
	10 20 30 40 50 60 MAESAGASSF FPLVVLLLAG SGGSGPRGVQ ALLCACTSCL QANYTCETDG ACMVSIFNLD 70 80 90 100 110 120 GMEHHVRTCI PKVELVPAGK PFYCLSSEDL RNTHCCYTDY CNRIDLRVPS GHLKEPEHPS 130 140 150 160 170 180 MWGPVELVGI IAGPVFLLFL IIIIVFLVIN YHQRVYHNRQ RLDMEDPSCE MCLSKDKTLQ 190 200 210 220 230 240 DLVYDLSTSG SGSGLPLFVQ RTVARTIVLQ EIIGKGRFGE VWRGRWRGGD VAVKIFSSRE 250 260 270 280 290 300 ERSWFREAEI YQTVMLRHEN ILGFIAADNK DNGTWTQLWL VSDYHEHGSL FDYLNRYTVT 310 320 330 340 350 360 IEGMIKLALS AASGLAHLHM EIVGTQGKPG IAHRDLKSKN ILVKKNGMCA IADLGLAVRH 370 380 390 400 410 420 DAVTDTIDIA PNQRVGTKRY MAPEVLDETI NMKHFDSFKC ADIYALGLVY WEIARRCNSG 430 440 450 460 470 480 GVHEEYQLPY YDLVPSDPSI EEMRKVVCDQ KLRPNIPNWW QSYEALRVMG KMMRECWYAN 490 500 GAARLTALRI KKTLSQLSVQ EDVKI
	Isoform 2 (SKR2-2). Checksum: 13269BD6D04F39D3	FASTA	476	53,411
	10 20 30 40 50 60 MAESAGASSF FPLVVLLLAG SGGSGPRGVQ ALLCACTSCL QANYTCETDG ACMVSIFNLD 70 80 90 100 110 120 GMEHHVRTCI PKVELVPAGK PFYCLSSEDL RNTHCCYTDY CNRIDLRVPS GHLKEPEHPS 130 140 150 160 170 180 MWGPVELVGI IAGPVFLLFL IIIIVFLVIN YHQRVYHNRQ RLDMEDPSCE MCLSKDKTLQ 190 200 210 220 230 240 DLVYDLSTSG SGSGLPLFVQ RTVARTIVLQ EIIGKGRFGE VWRGRWRGGD VAVKIFSSRE 250 260 270 280 290 300 ERSWFREAEI YQTVMLRHEN ILGFIAADNK DNGTWTQLWL VSDYHEHGSL FDYLNRYTVT 310 320 330 340 350 360 IEGMIKLALS AASGLAHLHM EIVGTQGKPG IAHRDLKSKN ILVKKNGMCA IADLGLAVRH 370 380 390 400 410 420 DAVTDTIDIA PNQRVGTKRY MAPEVLDETI NMKHFDSFKC ADIYALGLVY WEIARRCNSG 430 440 450 460 470 GVHEEYQLPY YDLVPSDPSI EEMRKVVCDQ KLRPNIPNWW QSYEVRSWPP AAFPSA
	Isoform 3 (SKR2-3). Checksum: 969525A044E8F7C6	FASTA	487	54,270
	10 20 30 40 50 60 MAESAGASSF FPLVVLLLAG SGGSGPRGVQ ALLCACTSCL QANYTCETDG ACMVSIFNLD 70 80 90 100 110 120 GMEHHVRTCI PKVELVPAGK PFYCLSSEDL RNTHCCYTDY CNRIDLRVPS GHLKEPEHPS 130 140 150 160 170 180 MWGPVELVGI IAGPVFLLFL IIIIVFLVIN YHQRVYHNRQ RLDMEDPSCE MCLSKDKTLQ 190 200 210 220 230 240 DLVYDLSTSG SGSGLPLFVQ RTVARTIVLQ EIIGKGRFGE VWRGRWRGGD VAVKIFSSRE 250 260 270 280 290 300 ERSWFREAEI YQTVMLRHEN ILGFIAADNK DNGTWTQLWL VSDYHEHGSL FDYLNRYTVT 310 320 330 340 350 360 IEGMIKLALS AASGLAHLHM EIVGTQGKPG IAHRDLKSKN ILVKKNGMCA IADLGLAVRH 370 380 390 400 410 420 DAVTDTIDIA PNQRVGTKRY MAPEVLDETI NMKHFDSFKC ADIYALGLVY WEIARRCNSG 430 440 450 460 470 480 GTFLFCLCSY LPFQDAGSPK AVLLPPFFLQ PVGCLLPEPE SSFKVAIKGV EVAVLRVRLF FRDQFVE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity." ten Dijke P., Ichijo H., Franzen P., Schulz P., Saras J., Toyoshima H., Heldin C.-H., Miyazono K. Oncogene 8:2879-2887(1993) [PubMed: 8397373] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin." Carcamo J., Weis F.M., Ventura F., Wieser R., Wrana J.L., Attisano L., Massague J. Mol. Cell. Biol. 14:3810-3821(1994) [PubMed: 8196624] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[3]	"Genomic structure and cloned cDNAs predict that four variants in the kinase domain of serine/threonine kinase receptors arise by alternative splicing and poly(A) addition." Xu J., Matsuzaki K., McKeehan K., Wang F., Kan M., McKeehan W.L. Proc. Natl. Acad. Sci. U.S.A. 91:7957-7961(1994) [PubMed: 8058741] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING. Tissue: Liver.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Eye.
[6]	"Identification of the phosphotyrosine proteome from thrombin activated platelets." Maguire P.B., Wynne K.J., Harney D.F., O'Donoghue N.M., Stephens G., Fitzgerald D.J. Proteomics 2:642-648(2002) [PubMed: 12112843] [Abstract] Cited for: PHOSPHORYLATION AT TYR-380.
[7]	"Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination." Esguerra C.V., Nelles L., Vermeire L., Ibrahimi A., Crawford A.D., Derua R., Janssens E., Waelkens E., Carmeliet P., Collen D., Huylebroeck D. Development 134:4381-4393(2007) [PubMed: 18039968] [Abstract] Cited for: FUNCTION, AUTOPHOSPHORYLATION.
[8]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-146, VARIANT [LARGE SCALE ANALYSIS] HIS-478 (ISOFORM 3).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	Z22536 mRNA. Translation: CAA80258.1. U14722 mRNA. Translation: AAA50246.1. L10125 mRNA. Translation: AAA60555.1. L10126 mRNA. Translation: AAA60556.1. L31848 Genomic DNA. Translation: AAA53349.1. L31848 Genomic DNA. Translation: AAA53350.1. L31848 Genomic DNA. Translation: AAA53351.1. BT007072 mRNA. Translation: AAP35735.1. BC000254 mRNA. Translation: AAH00254.1. BC040531 mRNA. Translation: AAH40531.1.
IPI	IPI00005732. IPI00218980. IPI00297220.
PIR	I38859. I80182. I80183.
RefSeq	NP_004293.1. NP_064732.2. NP_064733.2.
UniGene	Hs.438918
3D structure databases
HSSP	HSSP built from PDB template 1B6C based on UniProtKB P36897.
SMR	P36896. Positions 173-501.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:427N.
STRING	P36896.
Proteomic databases
PRIDE	P36896.
Genome annotation databases
Ensembl	ENST00000257963; ENSP00000257963; ENSG00000135503; Homo sapiens. [Genome view] ENST00000415850; ENSP00000397550; ENSG00000135503; Homo sapiens. [Genome view] ENST00000426655; ENSP00000390477; ENSG00000135503; Homo sapiens. [Genome view]
GeneID	91.
KEGG	hsa:91.
UCSC	uc001rzl.1. human. uc001rzm.1. human. uc001rzn.1. human.
Organism-specific databases
CTD	91.
GeneCards	GC12P050631.
H-InvDB	HIX0010648.
HGNC	HGNC:172. ACVR1B.
MIM	601300. gene.
PharmGKB	PA24493.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P36896.
HOVERGEN	P36896.
OMA	SSWGPVE.
Enzyme and pathway databases
BRENDA	2.7.10.2. 247. 2.7.11.30. 247.
Gene expression databases
ArrayExpress	P36896.
Bgee	P36896.
CleanEx	HS_ACVR1B.
Genevestigator	P36896.
Family and domain databases
InterPro	IPR000472. Activin_rcpt. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR003605. TGF_beta_rcpt_GS. [Graphical view]
Pfam	PF01064. Activin_recp. 1 hit. PF00069. Pkinase. 1 hit. PF08515. TGF_beta_GS. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00467. GS. 1 hit. [Graphical view]
PROSITE	PS51256. GS. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00171. Adenosine triphosphate.
NextBio	339.
SOURCE	Search...

Entry information

Entry name

ACV1B_HUMAN

Accession

Primary (citable) accession number: P36896
Secondary accession number(s): Q15479 , Q15480, Q15481, Q15482

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	November 3, 2009
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.