Q96B86 (RGMA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Repulsive guidance molecule A

Alternative name(s):
RGM domain family member A

Gene names

Name:	RGMA
Synonyms:	RGM

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	450 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	Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system. Regulates cephalic neural tube closure, inhibits neurite outgrowth and cortical neuron branching, and the formation of mature synapses. Binding to its receptor NEO1/neogenin induces activation of RHOA-ROCK1/Rho-kinase signaling pathway through UNC5B-ARHGEF12/LARG-PTK2/FAK1 cascade, leading to collapse of the neuronal growth cone and neurite outgrowth inhibition. Furthermore, RGMA binding to NEO1/neogenin leads to HRAS inactivation by influencing HRAS1-PTK2/FAK1-AKT1 pathway. It also functions as a bone morphogenetic protein (BMP) coreceptor that may signal through SMAD1, SMAD5, and SMAD8. Ref.7 Ref.8
Subunit structure	Interacts with NEO1, BMP2 and BMP4 By similarity.
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor By similarity.
Sequence similarities	Belongs to the repulsive guidance molecule (RGM) family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
PTM	GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Traceable author statement. Source: Reactome
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum Inferred from direct assay. Source: LIFEdb plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96B86-1)

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: Q96B86-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MQPP → ARGRGGRSLPARCSRRRSEAALSSQRDLFSSPFFLNSSS

Note: Incomplete sequence. No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 47	47	Potential
	Propeptide	48 – 168	121	Removed in mature form By similarity		PRO_0000030385
	Chain	169 – 424	256	Repulsive guidance molecule A		PRO_0000030386
	Propeptide	425 – 450	26	Removed in mature form Potential		PRO_0000030387
Amino acid modifications
	Lipidation	424	1	GPI-anchor amidated alanine Potential
	Glycosylation	114	1	N-linked (GlcNAc...) Potential
	Glycosylation	159	1	N-linked (GlcNAc...) Potential
	Glycosylation	389	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 4	4	MQPP → ARGRGGRSLPARCSRRRSEA ALSSQRDLFSSPFFLNSSS in isoform 2.		VSP_022294
	Natural variant	415	1	D → E. Ref.1 Ref.2 Ref.4 Ref.5 Ref.6 Corresponds to variant rs4238485 [ dbSNP | Ensembl ].		VAR_062144
	Natural variant	431	1	A → V. Corresponds to variant rs4778078 [ dbSNP | Ensembl ].		VAR_060105
Experimental info
	Sequence conflict	199	1	V → A in BAC11285. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: E3244FA43A029DCF	FASTA	450	49,347
	10 20 30 40 50 60 MQPPRERLVV TGRAGWMGMG RGAGRSALGF WPTLAFLLCS FPAATSPCKI LKCNSEFWSA 70 80 90 100 110 120 TSGSHAPASD DTPEFCAALR SYALCTRRTA RTCRGDLAYH SAVHGIEDLM SQHNCSKDGP 130 140 150 160 170 180 TSQPRLRTLP PAGDSQERSD SPEICHYEKS FHKHSATPNY THCGLFGDPH LRTFTDRFQT 190 200 210 220 230 240 CKVQGAWPLI DNNYLNVQVT NTPVLPGSAA TATSKLTIIF KNFQECVDQK VYQAEMDELP 250 260 270 280 290 300 AAFVDGSKNG GDKHGANSLK ITEKVSGQHV EIQAKYIGTT IVVRQVGRYL TFAVRMPEEV 310 320 330 340 350 360 VNAVEDWDSQ GLYLCLRGCP LNQQIDFQAF HTNAEGTGAR RLAAASPAPT APETFPYETA 370 380 390 400 410 420 VAKCKEKLPV EDLYYQACVF DLLTTGDVNF TLAAYYALED VKMLHSNKDK LHLYDRTRDL 430 440 450 PGRAAAGLPL APRPLLGALV PLLALLPVFC
	Isoform 2 [UniParc]. Checksum: F0B61FB890E8D2BE	FASTA	485	53,147
	10 20 30 40 50 60 ARGRGGRSLP ARCSRRRSEA ALSSQRDLFS SPFFLNSSSR ERLVVTGRAG WMGMGRGAGR 70 80 90 100 110 120 SALGFWPTLA FLLCSFPAAT SPCKILKCNS EFWSATSGSH APASDDTPEF CAALRSYALC 130 140 150 160 170 180 TRRTARTCRG DLAYHSAVHG IEDLMSQHNC SKDGPTSQPR LRTLPPAGDS QERSDSPEIC 190 200 210 220 230 240 HYEKSFHKHS ATPNYTHCGL FGDPHLRTFT DRFQTCKVQG AWPLIDNNYL NVQVTNTPVL 250 260 270 280 290 300 PGSAATATSK LTIIFKNFQE CVDQKVYQAE MDELPAAFVD GSKNGGDKHG ANSLKITEKV 310 320 330 340 350 360 SGQHVEIQAK YIGTTIVVRQ VGRYLTFAVR MPEEVVNAVE DWDSQGLYLC LRGCPLNQQI 370 380 390 400 410 420 DFQAFHTNAE GTGARRLAAA SPAPTAPETF PYETAVAKCK EKLPVEDLYY QACVFDLLTT 430 440 450 460 470 480 GDVNFTLAAY YALEDVKMLH SNKDKLHLYD RTRDLPGRAA AGLPLAPRPL LGALVPLLAL LPVFC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLU-415. Tissue: Testis.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLU-415. Tissue: Teratocarcinoma.
[3]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-415.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLU-415. Tissue: Brain and Uterus.
[6]	The European IMAGE consortium Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLU-415. Tissue: Retina.
[7]	"Unc5B associates with LARG to mediate the action of repulsive guidance molecule." Hata K., Kaibuchi K., Inagaki S., Yamashita T. J. Cell Biol. 184:737-750(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Inactivation of Ras by p120GAP via focal adhesion kinase dephosphorylation mediates RGMa-induced growth cone collapse." Endo M., Yamashita T. J. Neurosci. 29:6649-6662(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL136826 mRNA. Translation: CAB66760.1. AK074910 mRNA. Translation: BAC11285.1. AK074966 mRNA. Translation: BAC11321.1. AK074980 mRNA. Translation: BAC11330.1. AC087641 Genomic DNA. No translation available. CH471101 Genomic DNA. Translation: EAX02167.1. BC015886 mRNA. Translation: AAH15886.2. BC140838 mRNA. Translation: AAI40839.1. BC151132 mRNA. Translation: AAI51133.1. AL390083 mRNA. Translation: CAB98207.1.
IPI	IPI00015049. IPI00478417.
RefSeq	NP_001159758.1. NM_001166286.1. NP_001159759.1. NM_001166287.1. NP_001159760.1. NM_001166288.1. NP_001159761.1. NM_001166289.1. NP_064596.2. NM_020211.2.
UniGene	Hs.271277.
3D structure databases
ProteinModelPortal	Q96B86.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96B86. 2 interactions.
MINT	MINT-1420050.
STRING	9606.ENSP00000330005.
PTM databases
PhosphoSite	Q96B86.
Polymorphism databases
DMDM	296452979.
Proteomic databases
PaxDb	Q96B86.
PRIDE	Q96B86.
Protocols and materials databases
DNASU	56963.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000329082; ENSP00000330005; ENSG00000182175.
GeneID	56963.
KEGG	hsa:56963.
UCSC	uc002bsq.2. human.
Organism-specific databases
CTD	56963.
GeneCards	GC15M093586.
HGNC	HGNC:30308. RGMA.
HPA	CAB012343.
MIM	607362. gene.
neXtProt	NX_Q96B86.
PharmGKB	PA128394693.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG87951.
HOVERGEN	HBG057627.
InParanoid	Q96B86.
KO	K06847.
OrthoDB	EOG4001JB.
Enzyme and pathway databases
Pathway_Interaction_DB	bmppathway. BMP receptor signaling.
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
ArrayExpress	Q96B86.
Bgee	Q96B86.
CleanEx	HS_RGMA.
Genevestigator	Q96B86.
GermOnline	ENSG00000182175. Homo sapiens.
Family and domain databases
InterPro	IPR009496. RGM_C. IPR010536. RGM_N. [Graphical view]
Pfam	PF06534. RGM_C. 1 hit. PF06535. RGM_N. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	RGMA. human.
GenomeRNAi	56963.
NextBio	62595.
SOURCE	Search...

Entry information

Entry name

RGMA_HUMAN

Accession

Primary (citable) accession number: Q96B86
Secondary accession number(s): B2RTW1 , Q0JV97, Q8NC80, Q9H0E6, Q9NPM3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	May 18, 2010
Last modified:	April 3, 2013
This is version 80 of the entry and version 3 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.